{"results":[{"id":"arxiv_2601.08147","title":"Network Pharmacology Framework Characterizes Polypharmacological Properties of Dietary Flavonoids: Integration of Computational, Experimental, and Epidemiological Evidence","authors":[{"name":"Koyo Fujisaki"},{"name":"Osei Horikoshi"},{"name":"Yukitoshi Nagahara"},{"name":"Kengo Morohashi"}],"abstract":"Dietary flavonoids associate with disease prevention in epidemiological studies, yet their polypharmacological mechanisms remain unclear. We establish network pharmacology as a systematic framework to characterize flavonoid therapeutic properties through integrated computational, experimental, and epidemiological validation. We constructed a master network of 17,869 human proteins, 14 dietary flavonoids, and 1,496 FDA-approved drugs with 278,768 interactions. Flavonoids averaged 45.3 target proteins per compound compared to 16.8 for FDA-approved drugs (2.7-fold higher; p=7.5x10^-4), reflecting multi-target architecture. Statistical analysis revealed that 71.4% of flavonoids targeted proteins associated with cardiovascular drugs and 78.6% aligned with antineoplastic drug targets. MTT-based Jurkat cell assays confirmed network predictions: high-association flavonoids (luteolin LC50=31.4 microM, myricetin=29.5 microM) produced strong cytotoxicity, while low-association flavonoids showed minimal activity (LC50\u003e200 microM). Network-predicted association strengths correlated with experimental bioactivity (Pearson r=0.918; R^2=0.843). We translated network associations into food-level predictions across 506 foods, identifying 685 food-drug therapeutic combinations. Systematic literature searches confirmed 96 associations supported by 132 unique references. Cardiovascular domains achieved 47.1% validation. Top-validated foods included tea (31 evidence items), blueberries (18 items), tomato (13 items), grape juice (10 items), and plum (9 items). Network pharmacology characterizes dietary polypharmacological properties and generates evidence-based food-therapeutic predictions, bridging nutritional science and systems pharmacology.","source":"arXiv","year":2026,"language":"en","subjects":["q-bio.QM","q-bio.BM"],"url":"https://arxiv.org/abs/2601.08147","pdf_url":"https://arxiv.org/pdf/2601.08147","is_open_access":true,"published_at":"2026-01-13T02:21:48Z","score":70},{"id":"arxiv_2603.03407","title":"Tracing Pharmacological Knowledge In Large Language Models","authors":[{"name":"Basil Hasan Khwaja"},{"name":"Dylan Chen"},{"name":"Guntas Toor"},{"name":"Anastasiya Kuznetsova"}],"abstract":"Large language models (LLMs) have shown strong empirical performance across pharmacology and drug discovery tasks, yet the internal mechanisms by which they encode pharmacological knowledge remain poorly understood. In this work, we investigate how drug-group semantics are represented and retrieved within Llama-based biomedical language models using causal and probing-based interpretability methods. We apply activation patching to localize where drug-group information is stored across model layers and token positions, and complement this analysis with linear probes trained on token-level and sum-pooled activations. Our results demonstrate that early layers play a key role in encoding drug-group knowledge, with the strongest causal effects arising from intermediate tokens within the drug-group span rather than the final drug-group token. Linear probing further reveals that pharmacological semantics are distributed across tokens and are already present in the embedding space, with token-level probes performing near chance while sum-pooled representations achieve maximal accuracy. Together, these findings suggest that drug-group semantics in LLMs are not localized to single tokens but instead arise from distributed representations. This study provides the first systematic mechanistic analysis of pharmacological knowledge in LLMs, offering insights into how biomedical semantics are encoded in large language models.","source":"arXiv","year":2026,"language":"en","subjects":["cs.CL"],"url":"https://arxiv.org/abs/2603.03407","pdf_url":"https://arxiv.org/pdf/2603.03407","is_open_access":true,"published_at":"2026-03-03T17:04:08Z","score":70},{"id":"arxiv_2603.01537","title":"Pharmacology Knowledge Graphs: Do We Need Chemical Structure for Drug Repurposing?","authors":[{"name":"Youssef Abo-Dahab"},{"name":"Ruby Hernandez"},{"name":"Ismael Caleb Arechiga Duran"}],"abstract":"The contributions of model complexity, data volume, and feature modalities to knowledge graph-based drug repurposing remain poorly quantified under rigorous temporal validation. We constructed a pharmacology knowledge graph from ChEMBL 36 comprising 5,348 entities including 3,127 drugs, 1,156 proteins, and 1,065 indications. A strict temporal split was enforced with training data up to 2022 and testing data from 2023 to 2025, together with biologically verified hard negatives mined from failed assays and clinical trials. We benchmarked five knowledge graph embedding models and a standard graph neural network with 3.44 million parameters that incorporates drug chemical structure using a graph attention encoder and ESM-2 protein embeddings. Scaling experiments ranging from 0.78 to 9.75 million parameters and from 25 to 100 percent of the data, together with feature ablation studies, were used to isolate the contributions of model capacity, graph density, and node feature modalities. Removing the graph attention based drug structure encoder and retaining only topological embeddings combined with ESM-2 protein features improved drug protein PR-AUC from 0.5631 to 0.5785 while reducing VRAM usage from 5.30 GB to 353 MB. Replacing the drug encoder with Morgan fingerprints further degraded performance, indicating that explicit chemical structure representations can be detrimental for predicting pharmacological network interactions. Increasing model size beyond 2.44 million parameters yielded diminishing returns, whereas increasing training data consistently improved performance. External validation confirmed 6 of the top 14 novel predictions as established therapeutic indications. These results show that drug pharmacological behavior can be accurately predicted using target-centric information and drug network topology alone, without requiring explicit chemical structure representations.","source":"arXiv","year":2026,"language":"en","subjects":["cs.AI","q-bio.BM","q-bio.QM"],"url":"https://arxiv.org/abs/2603.01537","pdf_url":"https://arxiv.org/pdf/2603.01537","is_open_access":true,"published_at":"2026-03-02T07:07:32Z","score":70},{"id":"arxiv_2601.21643","title":"Computational investigation of single herbal drugs in Ayurveda for diabetes and obesity using knowledge graph and network pharmacology","authors":[{"name":"Priyotosh Sil"},{"name":"Rahul Tiwari"},{"name":"Vasavi Garisetti"},{"name":"Shanmuga Priya Baskaran"},{"name":"Fenita Hephzibah Dhanaseelan"},{"name":"Smita Srivastava"},{"name":"Areejit Samal"}],"abstract":"Metabolic diseases such as type 2 diabetes and obesity represent a rapidly escalating global health burden, yet current therapeutic strategies largely target isolated symptoms or single molecular pathways. To this end, we developed an integrated computational pipeline leveraging knowledge graph, pathway analysis and network pharmacology to elucidate the multi-target mechanisms of Ayurvedic Single Herbal Drugs (SHDs). SHDs associated with diabetes and obesity were curated from the Ayurvedic Pharmacopoeia of India, followed by phytochemical identification using IMPPAT database, yielding a shortlist of 11 SHDs and their 188 phytochemicals after drug-likeness and bioavailability filtering. Subsequently, molecular targets of the phytochemicals in SHDs, disease-associated genes and therapeutic targets of FDA-approved drugs, were curated via integration of data from several databases. Pathway enrichment analysis revealed significant functional overlap between SHD-associated and disease-associated pathways. All curated data were embedded into a Neo4j-based knowledge graph, enabling SHD-disease intersection analysis that prioritized key disease-relevant targets, including PTPN1, GLP1R, and DPP4. Also, the SHD-Target-FDA-approved drug profile elucidated the molecular and mechanistic aspects of the SHDs as a phytochemical cocktail, and is in alignment with the clinically studied synergistic FDA-approved drug combinations. Network pharmacology based protein-protein interaction analysis identified PPARG as another central regulator. Using a quantitative framework, we identified phytochemical pairs within SHDs, which were structurally dissimilar and target-wise distinct, yet acted on shared or different disease-associated pathways, indicating complementary and potentially synergistic interactions. Molecular docking analysis of two selected druggable targets identified putative lead phytochemicals.","source":"arXiv","year":2026,"language":"en","subjects":["q-bio.MN","q-bio.SC"],"url":"https://arxiv.org/abs/2601.21643","pdf_url":"https://arxiv.org/pdf/2601.21643","is_open_access":true,"published_at":"2026-01-29T12:45:43Z","score":70},{"id":"doaj_10.3389/fphar.2025.1700587","title":"Atrial fibrillation signals associated with overactive bladder drugs across JADER and FAERS: disproportionality and time-to-onset analyses","authors":[{"name":"Kyosuke Nagura"},{"name":"Satoko Watanabe"},{"name":"Taro Watanabe"},{"name":"Taro Watanabe"},{"name":"Hidenori Sagara"},{"name":"Hidenori Sagara"}],"abstract":"IntroductionOveractive bladder (OAB) drugs are widely prescribed, yet the occurrence of atrial fibrillation (AF) after treatment initiation remains poorly characterized.MethodsWe evaluated reports of AF associated with OAB medications using two spontaneous reporting systems (SRSs): the Japanese Adverse Drug Event Report (JADER) database and the U.S. FDA Adverse Event Reporting System (FAERS). We screened eight agents and assessed signals using three disproportionality metrics: the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). For drugs showing signals in both databases, we conducted stratified analyses by sex, age, and number of concomitant medications, and evaluated time-to-onset (TTO) using Weibull modeling.ResultsConsistent AF signals were identified for solifenacin succinate and mirabegron, whereas other agents did not meet the prespecified criteria. Solifenacin met the criteria in women and older adults in both JADER and FAERS. Mirabegron met the criteria across multiple strata in both datasets, indicating cross-stratum reproducibility. TTO was right‐skewed, with most reports occurring within one year of initiation. Exploratory Weibull modeling, based on limited numbers of date‐complete reports, suggested a wear-out pattern for solifenacin in JADER and an early pattern in FAERS, while mirabegron showed a random pattern in JADER and an early pattern in FAERS. These failure‐type patterns should therefore be interpreted cautiously.DiscussionThese findings are hypothesis-generating, given the limitations of SRSs, such as underreporting, missing dates, and unknown exposure—and they reflect reporting patterns rather than causal risk. They outline strata and early treatment periods that may warrant clinical attention and help prioritize pharmacovigilance and targeted hypothesis‐driven evaluation in routine OAB care.","source":"DOAJ","year":2026,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.3389/fphar.2025.1700587","url":"https://www.frontiersin.org/articles/10.3389/fphar.2025.1700587/full","is_open_access":true,"published_at":"","score":70},{"id":"arxiv_2503.04069","title":"Integrating network pharmacology, metabolomics, and gut microbiota analysis to explore the effects of Jinhong tablets on chronic superficial gastritis","authors":[{"name":"Lihao Xiao"},{"name":"Tingyu Zhang"},{"name":"Yun Liu"},{"name":"Chayanis Sutcharitchan"},{"name":"Qingyuan Liu"},{"name":"Xiaoxue Fan"},{"name":"Jian Feng"},{"name":"Huifang Gao"},{"name":"Tong Zhang"},{"name":"Shao Li"}],"abstract":"Chronic superficial gastritis (CSG) severely affects quality of life and can progress to worse gastric pathologies. Traditional Chinese Medicine (TCM) effectively treats CSG, as exemplified by Jinhong Tablets (JHT) with known anti-inflammatory properties, though their mechanism remains unclear. This study integrated network pharmacology, untargeted metabolomics, and gut microbiota analyses to investigate how JHT alleviates CSG. A rat CSG model was established and evaluated via H\u0026E staining. We identified JHT's target profiles and constructed a multi-layer biomolecular network. Differential metabolites in plasma were determined by untargeted metabolomics, and gut microbiota diversity/composition in fecal and cecal samples was assessed via 16S rRNA sequencing. JHT markedly reduced gastric inflammation. Network pharmacology highlighted metabolic pathways, particularly lipid and nitric oxide metabolism, as essential to JHT's therapeutic effect. Metabolomics identified key differential metabolites including betaine (enhancing gut microbiota), phospholipids, and citrulline (indicating severity of CSG). Pathway enrichment supported the gut microbiota's involvement. Further microbiota analysis showed that JHT increased betaine abundance, improved short-chain fatty acid production, and elevated Faecalibaculum and Bifidobacterium, thereby alleviating gastric inflammation. In conclusion, JHT alleviates CSG via diverse metabolic processes, especially lipid and energy metabolism, and influences metabolites like betaine alongside gut microbes such as Faecalibaculum and Bifidobacterium. These findings underscore JHT's therapeutic potential and deepen our understanding of TCM's role in CSG management.","source":"arXiv","year":2025,"language":"en","subjects":["q-bio.MN"],"url":"https://arxiv.org/abs/2503.04069","pdf_url":"https://arxiv.org/pdf/2503.04069","is_open_access":true,"published_at":"2025-03-06T04:05:37Z","score":69},{"id":"arxiv_2504.06196","title":"TxGemma: Efficient and Agentic LLMs for Therapeutics","authors":[{"name":"Eric Wang"},{"name":"Samuel Schmidgall"},{"name":"Paul F. Jaeger"},{"name":"Fan Zhang"},{"name":"Rory Pilgrim"},{"name":"Yossi Matias"},{"name":"Joelle Barral"},{"name":"David Fleet"},{"name":"Shekoofeh Azizi"}],"abstract":"Therapeutic development is a costly and high-risk endeavor that is often plagued by high failure rates. To address this, we introduce TxGemma, a suite of efficient, generalist large language models (LLMs) capable of therapeutic property prediction as well as interactive reasoning and explainability. Unlike task-specific models, TxGemma synthesizes information from diverse sources, enabling broad application across the therapeutic development pipeline. The suite includes 2B, 9B, and 27B parameter models, fine-tuned from Gemma-2 on a comprehensive dataset of small molecules, proteins, nucleic acids, diseases, and cell lines. Across 66 therapeutic development tasks, TxGemma achieved superior or comparable performance to the state-of-the-art generalist model on 64 (superior on 45), and against state-of-the-art specialist models on 50 (superior on 26). Fine-tuning TxGemma models on therapeutic downstream tasks, such as clinical trial adverse event prediction, requires less training data than fine-tuning base LLMs, making TxGemma suitable for data-limited applications. Beyond these predictive capabilities, TxGemma features conversational models that bridge the gap between general LLMs and specialized property predictors. These allow scientists to interact in natural language, provide mechanistic reasoning for predictions based on molecular structure, and engage in scientific discussions. Building on this, we further introduce Agentic-Tx, a generalist therapeutic agentic system powered by Gemini 2.5 that reasons, acts, manages diverse workflows, and acquires external domain knowledge. Agentic-Tx surpasses prior leading models on the Humanity's Last Exam benchmark (Chemistry \u0026 Biology) with 52.3% relative improvement over o3-mini (high) and 26.7% over o3-mini (high) on GPQA (Chemistry) and excels with improvements of 6.3% (ChemBench-Preference) and 2.4% (ChemBench-Mini) over o3-mini (high).","source":"arXiv","year":2025,"language":"en","subjects":["cs.AI","cs.CL","cs.LG"],"url":"https://arxiv.org/abs/2504.06196","pdf_url":"https://arxiv.org/pdf/2504.06196","is_open_access":true,"published_at":"2025-04-08T16:39:02Z","score":69},{"id":"doaj_10.1530/REM-25-0001","title":"Heme iron amplifies azoxymethane initiating effect on rat colon preneoplastic lesions","authors":[{"name":"Julia Keller"},{"name":"Pascale Plaisancié"},{"name":"Edwin Fouché"},{"name":"Edwige-Marie Pralet"},{"name":"Nathalie Naud"},{"name":"Florence Blas-Y-Estrada"},{"name":"Claire Maslo"},{"name":"Ingrid Ahn"},{"name":"Sylvie Chevolleau"},{"name":"Maria-Helena Meireles"},{"name":"Cécile Héliès-Toussaint"},{"name":"Sylvia Pietri"},{"name":"Mathieu Cassien"},{"name":"Laure Khoury"},{"name":"Marc Audebert"},{"name":"Fabrice Pierre"},{"name":"Vassilia Theodorou"},{"name":"Maïwenn Olier"},{"name":"Françoise Guéraud"}],"abstract":"Objective: Colorectal cancer is a major public health issue for which dietary factors such as red and processed meat consumption seem to play a prominent role. Heme iron, which is present in important concentration in those food products, was reported to play a role in colorectal cancer promotion in animal studies. However, its role in colorectal cancer initiation remains to be established. Methods: Male Fischer 344 rats were given experimental diets (control diet, ferric citrate-supplemented diet or hemin-supplemented diet) for 2 weeks before being initiated for colon cancer with azoxymethane. Rats were then fed a control diet for 8 weeks. Preneoplastic lesions, lipid peroxidation, genotoxicity and oxidative stress markers, together with gut microbiota, were analyzed. Results: Heme iron, given in the rat diet for only 2 weeks before the colorectal cancer initiating event, increased two types of preneoplastic lesions in the rat colon, namely aberrant crypt foci and mucin-depleted foci, when compared to a control diet containing the same amount of iron in a non-heminic form. This heme iron concentration in the diet, representative of human consumption, induced at the same time a huge increase in luminal lipid peroxidation, a significant increase in RNA/DNA oxidative damage and an increase in the expression of antioxidant defenses in colon mucosa, accompanied by epithelial cell proliferation together with a reduction in colon mucus cells, and a gut dysbiosis. Conclusion: These results, obtained in an animal model, suggest that iron, only in its heminic form, has a co-initiating effect on colorectal carcinogenesis.","source":"DOAJ","year":2025,"language":"","subjects":["Physiology","Therapeutics. Pharmacology"],"doi":"10.1530/REM-25-0001","url":"https://rem.bioscientifica.com/view/journals/rem/2025/1/REM-25-0001.xml","is_open_access":true,"published_at":"","score":69},{"id":"doaj_10.3389/fphar.2025.1689663","title":"Fedratinib reveals chemotherapeutic potential in esophageal squamous cell cancer","authors":[{"name":"Man Luo"},{"name":"Man Luo"},{"name":"Man Luo"},{"name":"Jiang Zhu"},{"name":"Jiang Zhu"},{"name":"Yong Yang"},{"name":"Yong Yang"},{"name":"Chongbo Liao"},{"name":"Chongbo Liao"},{"name":"Xiao Liu"},{"name":"Xiao Liu"},{"name":"Maoju Tang"},{"name":"Maoju Tang"},{"name":"Lei Xu"},{"name":"Xiaowu Zhong"},{"name":"Xiaowu Zhong"},{"name":"Qiang Ma"},{"name":"Qiang Ma"},{"name":"Xiaolan Guo"},{"name":"Xiaolan Guo"}],"abstract":"BackgroundDrug repurposing has emerged as a promising approach for discovering novel anticancer therapeutics. In this study, we systematically investigated the antitumor potential of fedratinib, a JAK2 inhibitor approved for myelofibrosis, against esophageal squamous cell carcinoma (ESCC) using integrated in vitro, in vivo, and patient-derived organoid (PDO) models. We further explored its underlying mechanisms of action.MethodsESCC cell lines (Eca109 and KYSE150) were treated with fedratinib to evaluate its effects on proliferation, migration, apoptosis, and cell cycle distribution. Molecular changes were examined using RT-qPCR and Western blot analyses. Antitumor efficacy was further validated in subcutaneous xenograft models and ESCC PDOs. Mechanistic investigations included STAT3 overexpression and functional rescue experiments.ResultsFedratinib significantly inhibited ESCC cell proliferation and migration and induced cell cycle arrest at the G2/M phase while promoting apoptosis in vitro. It also suppressed tumor growth in xenograft models and showed consistent efficacy in PDOs. Mechanistically, fedratinib inhibited the activation of the JAK2/STAT3 signaling pathway and downregulated the expression of vimentin, survivin, and cyclin D1. Overexpression of STAT3 reversed these molecular alterations and diminished the functional effects of fedratinib. Similarly, ectopic expression of survivin, vimentin, or cyclin D1 partially rescued the phenotypic changes induced by fedratinib.ConclusionFedratinib exerts antitumor effects against ESCC in vitro, in vivo, and in patient-derived organoid models by suppressing the JAK2–STAT3 signaling axis and its downstream effectors, vimentin, survivin, and cyclin D1.","source":"DOAJ","year":2025,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.3389/fphar.2025.1689663","url":"https://www.frontiersin.org/articles/10.3389/fphar.2025.1689663/full","is_open_access":true,"published_at":"","score":69},{"id":"arxiv_2402.14617","title":"The affinity-efficacy problem: an essential part of pharmacology education","authors":[{"name":"James P Higham"},{"name":"David Colquhoun"}],"abstract":"A fundamental mistake in receptor theory has led to an enduring misunderstanding of how to estimate the affinity and efficacy of an agonist. These properties are inextricably linked and cannot be easily separated in any case where the binding of a ligand induces a conformation change in its receptor. Consequently, binding curves and concentration-response relationships for receptor agonists have no straightforward interpretation. This problem, the affinity-efficacy problem, remains overlooked and misunderstood despite it being recognised in 1987. To avoid the further propagation of this misunderstanding, we propose that the affinity-efficacy problem should be included in the core curricula for pharmacology undergraduates proposed by the British Pharmacological Society and IUPHAR.","source":"arXiv","year":2024,"language":"en","subjects":["q-bio.OT"],"doi":"10.1098/rsos.240487","url":"https://arxiv.org/abs/2402.14617","pdf_url":"https://arxiv.org/pdf/2402.14617","is_open_access":true,"published_at":"2024-02-21T18:39:04Z","score":68},{"id":"doaj_10.1186/s12950-024-00402-0","title":"Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue","authors":[{"name":"Isobel C. Mouat"},{"name":"Li Zhu"},{"name":"Alperen Aslan"},{"name":"Barry W. McColl"},{"name":"Stuart M. Allan"},{"name":"Craig J. Smith"},{"name":"Marion S. Buckwalter"},{"name":"Laura McCulloch"}],"abstract":"Abstract Background Fatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke. Aims We performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue. Methods In a chronic ischemic stroke cohort (\u003e 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F \u003c 40) and low fatigue (FACIT-F \u003e 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data. Results We observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288). Conclusions These data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.","source":"DOAJ","year":2024,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.1186/s12950-024-00402-0","url":"https://doi.org/10.1186/s12950-024-00402-0","is_open_access":true,"published_at":"","score":68},{"id":"doaj_10.3390/antibiotics13030242","title":"Assessing the Microbial Quality of Shrimp (\u003ci\u003eXiphonaeus kroyeri)\u003c/i\u003e and Mussels (\u003ci\u003ePerna perna\u003c/i\u003e) Illegally Sold in the Vitória Region, Brazil, and Investigating the Antimicrobial Resistance of \u003ci\u003eEscherichia coli\u003c/i\u003e Isolates","authors":[{"name":"Daniella Tosta Link"},{"name":"Gustavo Guimarães Fernandes Viana"},{"name":"Lívia Pasolini Siqueira"},{"name":"Carolina Magri Ferraz"},{"name":"Romário Alves Rodrigues"},{"name":"Luis Antonio Mathias"},{"name":"Marita Vedovelli Cardozo"},{"name":"Gabriel Augusto Marques Rossi"}],"abstract":"The consumption of seafood is crucial for food security, but poor hygiene along the food production chain can result in low microbiological quality, posing significant risks for public health and seafood quality. Thus, this study aimed to assess the microbiological quality and antimicrobial sensitivity of \u003ci\u003eE. coli\u003c/i\u003e from 69 samples of illegally marketed shrimp and mussels in the Vitória Region, Brazil. These foods exhibited poor microbiological quality due to high counts of mesophilic, psychrotrophic, and enterobacteria microorganisms. While this issue is widespread in this area, shrimp samples displayed higher microbial counts compared to mussels, and fresh mussels had elevated counts of enterobacteria compared to frozen ones. Among the 10 \u003ci\u003eE. coli\u003c/i\u003e isolates, none carried the genes \u003ci\u003eblaCTX-M-1\u003c/i\u003e, \u003ci\u003eblaCTX-M-2\u003c/i\u003e, \u003ci\u003eblaCTX-M-3\u003c/i\u003e, \u003ci\u003eblaCTX-M-15\u003c/i\u003e, \u003ci\u003emcr-1\u003c/i\u003e, \u003ci\u003emcr-2\u003c/i\u003e, \u003ci\u003emcr-3\u003c/i\u003e, \u003ci\u003emcr-4\u003c/i\u003e, and \u003ci\u003etet\u003c/i\u003e, associated with antibiotic resistance. Phenotypical resistance to tetracycline and fosfomycin was not observed in any isolate, while only 20% demonstrated resistance to ciprofloxacin. Regarding ampicillin and amoxicillin with clavulanic acid, 60% of isolates were resistant, 10% showed intermediate susceptibility, and 30% were sensitive. One isolate was considered simultaneously resistant to β-lactams and quinolones, and none were conserved as ESBL producers. These findings highlight the inherent risks to local public health that arise from consuming improperly prepared seafood in this area.","source":"DOAJ","year":2024,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.3390/antibiotics13030242","url":"https://www.mdpi.com/2079-6382/13/3/242","is_open_access":true,"published_at":"","score":68},{"id":"doaj_10.2340/jrm.v55.5575","title":"End-of-life decisions and involvement of Physical and Rehabilitation Medicine Physicians in Europe","authors":[{"name":"Rutger Osterthun"},{"name":"Katharina Sunnerhagen"},{"name":"Henk J. Stam"},{"name":"Carlotte Kiekens"}],"abstract":"\nObjective: As Physical and Rehabilitation Medicine physicians are experts in functional prognoses of disabling health conditions, the aim of this study was to gain insight into their involvement in end-of-life decisions in patients with neurological or terminal diseases in European countries.\nDesign: Exploratory cross-sectional survey.\nSubjects: Delegates of the Union of European Medical Specialists, Physical and Rehabilitation Medicine Section.\nMethods: In July 2020, a self-constructed survey was sent to 82 delegates from 38 European countries, who were asked to answer from the point of view of their country. Topics included the legal status of end-of-life decisions and the involvement of Physical and\nRehabilitation Medicine physicians in these decisions.\nResults: Between July 2020 and December 2020, 32 delegates from 28 countries completed the survey (response rate country level of 74%). If legal frameworks allow for these specific end-of-life decisions, involvement of Physical and Rehabilitation Medicine physicians was reported in 2 of 3 countries in euthanasia cases, 10 of 17 countries in non-treatment decision cases, and 13 of 16 countries in cases of intensified symptom management by the administration of drugs using potentially life-shortening doses.\nConclusion: Estimated involvement of Physical and Rehabilitation Medicine physicians in end-of-life decisions varied between European countries, even when legal frameworks allow for these decisions.\n\n\nLAY ABSTRACT\nEnd-of-life considerations may arise after severe disabling health conditions and lead to end-of-life decisions. As Physical and Rehabilitation Medicine physicians are experts in functional prognosis for patients with these health conditions, their expertise could be of value to consider in these decisions. Legal frameworks and attitudes towards end-of-life decisions differ between European countries. However, there is a lack of information on the involvement of Physical and Rehabilitation Medicine physicians in these decisions. Therefore, delegates of Physical and Rehabilitation Medicine physicians in European countries were surveyed on the legal status of end-of-life decisions and the involvement of Physical and Rehabilitation Medicine physicians. The responses of delegates from 28 countries suggested differences in involvement of Physical and Rehabilitation Medicine physicians in end-of-life decisions between European countries, even between countries with a legal status of these end-of-life decisions. In the light of the ageing population and a general tendency toward more liberal attitudes concerning end-of-life decisions in Europe, these findings could be of interest in order to optimize end-of-life care in the coming years.\n","source":"DOAJ","year":2023,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.2340/jrm.v55.5575","url":"https://medicaljournalssweden.se/jrm/article/view/5575","is_open_access":true,"published_at":"","score":67},{"id":"arxiv_2201.08894","title":"Reinforcement Learning for Personalized Drug Discovery and Design for Complex Diseases: A Systems Pharmacology Perspective","authors":[{"name":"Ryan K. Tan"},{"name":"Yang Liu"},{"name":"Lei Xie"}],"abstract":"Many multi-genic systemic diseases such as neurological disorders, inflammatory diseases, and the majority of cancers do not have effective treatments yet. Reinforcement learning powered systems pharmacology is a potentially effective approach to design personalized therapies for untreatable complex diseases. In this survey, state-of-the-art reinforcement learning methods and their latest applications to drug design are reviewed. The challenges on harnessing reinforcement learning for systems pharmacology and personalized medicine are discussed. Potential solutions to overcome the challenges are proposed. In spite of successful application of advanced reinforcement learning techniques to target-based drug discovery, new reinforcement learning strategies are needed to address systems pharmacology-oriented personalized de novo drug design.","source":"arXiv","year":2022,"language":"en","subjects":["q-bio.BM","cs.LG"],"url":"https://arxiv.org/abs/2201.08894","pdf_url":"https://arxiv.org/pdf/2201.08894","is_open_access":true,"published_at":"2022-01-21T21:29:46Z","score":66},{"id":"arxiv_2208.10228","title":"Review of Natural Language Processing in Pharmacology","authors":[{"name":"Dimitar Trajanov"},{"name":"Vangel Trajkovski"},{"name":"Makedonka Dimitrieva"},{"name":"Jovana Dobreva"},{"name":"Milos Jovanovik"},{"name":"Matej Klemen"},{"name":"Aleš Žagar"},{"name":"Marko Robnik-Šikonja"}],"abstract":"Natural language processing (NLP) is an area of artificial intelligence that applies information technologies to process the human language, understand it to a certain degree, and use it in various applications. This area has rapidly developed in the last few years and now employs modern variants of deep neural networks to extract relevant patterns from large text corpora. The main objective of this work is to survey the recent use of NLP in the field of pharmacology. As our work shows, NLP is a highly relevant information extraction and processing approach for pharmacology. It has been used extensively, from intelligent searches through thousands of medical documents to finding traces of adversarial drug interactions in social media. We split our coverage into five categories to survey modern NLP methodology, commonly addressed tasks, relevant textual data, knowledge bases, and useful programming libraries. We split each of the five categories into appropriate subcategories, describe their main properties and ideas, and summarize them in a tabular form. The resulting survey presents a comprehensive overview of the area, useful to practitioners and interested observers.","source":"arXiv","year":2022,"language":"en","subjects":["cs.CL","cs.LG","q-bio.BM"],"doi":"10.1124/pharmrev.122.000715","url":"https://arxiv.org/abs/2208.10228","pdf_url":"https://arxiv.org/pdf/2208.10228","is_open_access":true,"published_at":"2022-08-22T12:10:27Z","score":66},{"id":"arxiv_2207.05179","title":"Digital Therapeutics for Mental Health: Is Attrition the Achilles Heel?","authors":[{"name":"Adaora Nwosu"},{"name":"Samantha Boardman"},{"name":"Mustafa M. Husain"},{"name":"P. Murali Doraiswamy"}],"abstract":"Digit therapeutics are novel software devices that clinicians may utilize in delivering quality mental health care and ensuring positive outcomes. However, uptake of digital therapeutics and clinically tested software-based programs remains low. This article presents possible reasons for attrition and low engagement in clinical studies investigating digital therapeutics, analyses of studies in which engagement was high, and design constructs that may encourage user engagement. The aim is to shed light on the importance of real-world attrition data of digital therapeutics, and important characteristics of medical devices that have positively influenced user engagement. The findings presented in this article will be useful to relevant stakeholders and medical device experts tasked with addressing the gap between software medical design and user engagement present in digital therapeutic clinical trials.","source":"arXiv","year":2022,"language":"en","subjects":["cs.CY"],"url":"https://arxiv.org/abs/2207.05179","pdf_url":"https://arxiv.org/pdf/2207.05179","is_open_access":true,"published_at":"2022-07-06T02:23:15Z","score":66},{"id":"doaj_Genetic+and+Psychosocial+Risk+Factors+Associated+with+Suicide+Among+Community+Veterans%3A+Implications+for+Screening%2C+Treatment+and+Precision+Medicine","title":"Genetic and Psychosocial Risk Factors Associated with Suicide Among Community Veterans: Implications for Screening, Treatment and Precision Medicine","authors":[{"name":"Boscarino JA"},{"name":"Adams RE"},{"name":"Urosevich TG"},{"name":"Hoffman SN"},{"name":"Kirchner HL"},{"name":"Chu X"},{"name":"Shi W"},{"name":"Boscarino JJ"},{"name":"Dugan RJ"},{"name":"Withey CA"},{"name":"Figley CR"}],"abstract":"Joseph A Boscarino,1 Richard E Adams,2 Thomas G Urosevich,3 Stuart N Hoffman,4 H Lester Kirchner,1 Xin Chu,5 Weixing Shi,5 Joseph J Boscarino,6 Ryan J Dugan,1 Carrie A Withey,1 Charles R Figley7 1Department Population Health Sciences, Geisinger Clinic, Danville, PA, 17822, USA; 2Department Sociology, Kent State University, Kent, OH, 44242, USA; 3Ophthalmology Service, Geisinger Clinic, Mount Pocono, PA, 18344, USA; 4Department Sleep Medicine, Geisinger Clinic, Danville, PA, 17822, USA; 5Obesity Institute, Geisinger Clinic, Danville, PA, 17822, USA; 6Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, STC 7, Tampa, FL, 33606, USA; 7School of Social Work, Tulane University, New Orleans, LA, 70112, USACorrespondence: Joseph A BoscarinoDepartment Population Health Sciences, Geisinger Clinic, 100 N. Academy Ave., 44-00, Danville, PA, 17822, USATel +1 570-214-9825Email joseph.boscarino@gmail.comIntroduction: Since veteran suicide is a concern and our knowledge of predictive factors is still limited, our objective was to assess risk factors for suicide, including genetic factors, among deployed veterans.Methods: For this study, we surveyed 1730 veterans who were outpatients in a multi-hospital system in Pennsylvania. Altogether, 1041 veterans (60%) provided a DNA sample. The genetic risk variants investigated were within loci previously associated with PTSD and substance misuse, including CRHR1, CHRNA5, RORA, and FKBP5 genetic variations, which were used to calculate a polygenic risk score (range=0– 8, mean=3.6, SD=1.4).Results: Most veterans (56.2%) were deployed to Vietnam while significant numbers were deployed to Iraq, Afghanistan, and other post-Vietnam conflicts. Overall, 95.1% of the veterans were male, their mean age was 56.2 (SD=12), and 95.6% were Caucasian. Among the veterans, 24% had high combat exposure. The prevalence of lifetime suicidal thoughts was 11.3%. Additionally, 5.7% ever developed a suicide plan or attempted suicide in their lifetimes. Among those with a history of a lifetime suicide attempt or suicide plan, the PTSD genetic risk score was significantly higher (OR=3.96 vs 3.55, p=0.033), but for suicidal thoughts, this association was not significant (p=0.717). In multivariable analysis (MVA) logistic regression, significant predictors of attempting suicide or having a suicide plan were history of depression (OR=5.04, p\u003c 0.001), PTSD genetic risk score (OR=1.25, p=0.036), history of childhood abuse/neglect (OR=2.24, p=0.009), and lifetime marijuana use (OR= 1.56, p=0.020). Conversely, rural residence was protective for suicide risk (OR=0.49; p=0.031). For suicidal thoughts, in the MVA genetic risk score was not significant (p=0.697), but history of child abuse/neglect (p\u003c 0.001), history of depression (p\u003e 0.001), low psychological resilience (p=0.004), and lifetime marijuana use (p=0.022) were significant.Discussion: In this study, we identified genetic risk variants and other predictors for suicide among veterans that may have implications for future screening and clinical care. Further research is advised.Keywords: veterans, warzone deployment, suicide, genetic factors, patient screening, precision medicine","source":"DOAJ","year":2022,"language":"","subjects":["Therapeutics. Pharmacology"],"url":"https://www.dovepress.com/genetic-and-psychosocial-risk-factors-associated-with-suicide-among-co-peer-reviewed-fulltext-article-PGPM","is_open_access":true,"published_at":"","score":66},{"id":"doaj_10.3390/antiox11081522","title":"Flavanol-Rich Cocoa Supplementation Inhibits Mitochondrial Biogenesis Triggered by Exercise","authors":[{"name":"Jose Angel García-Merino"},{"name":"Beatriz de Lucas"},{"name":"Karen Herrera-Rocha"},{"name":"Diego Moreno-Pérez"},{"name":"Maria Gregoria Montalvo-Lominchar"},{"name":"Arantxa Fernández-Romero"},{"name":"Catalina Santiago"},{"name":"Margarita Pérez-Ruiz"},{"name":"Mar Larrosa"}],"abstract":"The potential role of cocoa supplementation in an exercise context remains unclear. We describe the effects of flavanol-rich cocoa supplementation during training on exercise performance and mitochondrial biogenesis. Forty-two male endurance athletes at the beginning of the training season received either 5 g of cocoa (425 mg of flavanols) or maltodextrin (control) daily for 10 weeks. Two different doses of cocoa (equivalent to 5 g and 15 g per day of cocoa for a 70 kg person) were tested in a mouse exercise training study. In the athletes, while both groups had improved exercise performance, the maximal aerobic speed increased only in the control group. A mitochondrial DNA analysis revealed that the control group responded to training by increasing the mitochondrial load whereas the cocoa group showed no increase. Oxidative stress was lower in the cocoa group than in the control group, together with lower interleukin-6 levels. In the muscle of mice receiving cocoa, we corroborated an inhibition of mitochondrial biogenesis, which might be mediated by the decrease in the expression of nuclear factor erythroid-2-related factor 2. Our study shows that supplementation with flavanol-rich cocoa during the training period inhibits mitochondrial biogenesis adaptation through the inhibition of reactive oxygen species generation without impacting exercise performance.","source":"DOAJ","year":2022,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.3390/antiox11081522","url":"https://www.mdpi.com/2076-3921/11/8/1522","is_open_access":true,"published_at":"","score":66},{"id":"doaj_10.3389/fphar.2022.826395","title":"In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity","authors":[{"name":"Andre Luis Dias Araujo Mazzari"},{"name":"Mariella Guimarães Lacerda"},{"name":"Flora Aparecida Milton"},{"name":"Flora Aparecida Milton"},{"name":"João Augusto Mulin Montechiari Machado"},{"name":"Simone Batista Pires Sinoti"},{"name":"Anne-Soulene Toullec"},{"name":"Patricia Marquez Rodrigues"},{"name":"Francisco de Assis Rocha Neves"},{"name":"Luiz Alberto Simeoni"},{"name":"Dâmaris Silveira"},{"name":"Jose Maria Prieto"},{"name":"Jose Maria Prieto"},{"name":"Jose Maria Prieto"}],"abstract":"Many medicinal plants species from European -such as Artemisia absinthium, Equisetum arvense, Lamium album, Malva sylvestris, Morus nigra, Passiflora incarnata, Frangula purshiana, and Salix alba- as well as Latin American traditions -such as Libidibia ferrea, Bidens pilosa, Casearia sylvestris, Costus spicatus, Monteverdia ilicifolia, Persea americana, Schinus terebinthifolia, Solidago chilensis, Syzygium cumini, Handroanthus impetiginosus, and Vernonanthura phosphorica- are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). We further investigated the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of Gamma-glutamyl transferase (GGT) in HepG2 cells. Our results demonstrate L. ferrea, C. sylvestris, M. ilicifolia, P. americana, S. terebinthifolia, S. cumini, V. phosphorica, E. arvense, P. incarnata, F. purshiana, and S. alba can significantly increase CYP3A4 mRNA gene expression in HepG2 cells. Only F. purshiana shown to do so likely via hPXR activation. P-gp activity was affected by L. ferrea, F. purshiana, S. terebinthifolia, and S. cumini. Total intracellular glutathione levels were significantly depleted by exposure to all extracts except S. alba and S. cumini This was accompanied by a lower GGT activity in the case of C. spicatus, P. americana, S. alba, and S. terebinthifolia, whilst L. ferrea, P. incarnata and F. purshiana increased it. Surprisingly, S. cumini aqueous extract drastically decreased GGT activity (−48%, p \u0026lt; 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines causes in vitro disturbances to key drug metabolism mechanisms. We recommend active pharmacovigilance for Libidibia ferrea (Mart.) L. P. Queiroz, Frangula purshiana Cooper, Schinus terebinthifolia Raddi, and Salix alba L. which were able to alter all targets in our preclinical study.","source":"DOAJ","year":2022,"language":"","subjects":["Therapeutics. Pharmacology"],"doi":"10.3389/fphar.2022.826395","url":"https://www.frontiersin.org/articles/10.3389/fphar.2022.826395/full","is_open_access":true,"published_at":"","score":66},{"id":"arxiv_2102.07610","title":"Application of Quantitative Systems Pharmacology to guide the optimal dosing of COVID-19 vaccines","authors":[{"name":"Mario Giorgi"},{"name":"Rajat Desikan"},{"name":"Piet H. van der Graaf"},{"name":"Andrzej M. Kierzek"}],"abstract":"Optimal use and distribution of Covid-19 vaccines involves adjustments of dosing. Due to the rapidly-evolving pandemic, such adjustments often need to be introduced before full efficacy data are available. As demonstrated in other areas of drug development, quantitative systems pharmacology (QSP) is well placed to guide such extrapolation in a rational and timely manner. Here we propose for the first time how QSP can be applied real time in the context of COVID-19 vaccine development.","source":"arXiv","year":2021,"language":"en","subjects":["q-bio.QM"],"doi":"10.1002/psp4.12700","url":"https://arxiv.org/abs/2102.07610","pdf_url":"https://arxiv.org/pdf/2102.07610","is_open_access":true,"published_at":"2021-02-15T15:52:41Z","score":65}],"total":989179,"page":1,"page_size":20,"sources":["CrossRef","arXiv","DOAJ"],"query":"Therapeutics. Pharmacology"}