Echinococcosis is a neglected tropical disease (NTD) caused by Echinococcus granulosus and Echinococcus multilocularis, the etiological agents of cystic and alveolar echinococcosis, respectively. These infections pose a significant public health burden, particularly in endemic regions. Cestodes lack key enzymes involved in lipid metabolism and must acquire lipids from their hosts. Fatty-acid binding proteins (FABPs), which mediate lipid trafficking and intracellular transport, have therefore emerged as essential and potentially druggable targets. In this study, we implemented an integrated virtual screening strategy combining ligand-based and structure-based approaches to identify novel FABP binders as potential therapeutic agents against Echinococcus spp. High-specificity screening of approximately 435,000 compounds yielded a limited number of prioritized in silico hits. Four compounds-hydrochlorothiazide, naratriptan, fenticonazole, and montelukast-were selected for experimental validation, prioritizing repurposing candidates. Fluorescence displacement assays confirmed that hydrochlorothiazide binds to three cestode FABPs (EgFABP1, EmFABP1, and EmFABP3), validating the predictive performance of the computational workflow. These findings support the value of parallel in silico screening strategies and drug repurposing approaches for the discovery of new therapeutic candidates against NTD.

To identify potential agents associated with the development of valvular heart diseases (VHD), we used Mendelian randomization and colocalization analyses to pinpoint genes significantly linked to VHD. A total of 324 genes were found to be positively associated with VHD, among which AGK and TLE5 demonstrated evidence of colocalization. Then, transcriptome data of aortic and mitral valve diseases were retrieved from GEO database. Based on the expression levels of AGK and TLE5, sequencing data for aortic and mitral valve diseases were stratified into 2 subtypes, respectively. Differentially expressed genes between these subtypes underwent KEGG pathway enrichment analysis. Molecular docking revealed that ergotamine and fosfomycin exhibited the highest binding affinities to AGK and TLE5, respectively. Then, FDA Adverse Event Reporting System database was used to corroborate the associations between the identified drugs and aortic and mitral valve diseases. Analysis of the FDA Adverse Event Reporting System database indicated reporting odds ratios of 13.82 [95% confidence interval (CI): 5.17-36.94] for ergotamine and 2.14 (95% CI: 0.69-6.63) for fosfomycin. For further validation, naratriptan and aztreonam were used as control drugs. The adjusted odds ratios for ergotamine and fosfomycin were 8.31 (95% CI: 1.61-38.39) and 2.96 (95% CI: 0.84-18.75), respectively, when compared with the control drugs. Finally, human aortic and mitral interstitial cells were isolated and transfected with AGK plasmid. After adding Ly294002 (inhibitor of PI3K-Akt), the Western blot results showed that AGK promoted the fibrosis of aortic and mitral interstitial cells by PI3K-Akt signaling pathway. In conclusion, ergotamine may contribute to the development of aortic and mitral valve diseases through the activation of AGK.

Accurate sex estimation is of utmost importance in forensic anthropology and bioarchaeology. Nevertheless, traditional methods are frequently influenced by confounding factors and biases specific to certain populations. This study aims to revolutionize sex classification methods for Asian populations through the innovative integration of Orthogonal Partial Least Squares (OPLS) for dimensionality reduction and Linear Discriminant Analysis (LDA) for evaluating mandibular metrics. A collection of dry mandibles, predominantly sourced from the late 19th century to minimize the influence of modern admixture, was analyzed, measuring 16 key parameters. OPLS was utilized to isolate sex-relevant variations, followed by univariate and multivariate LDA to achieve robust classification, with cross-validation performed to ensure reliability. The results indicated cross-validated accuracies ranging from 75.7 to 87.4% for univariate LDA and from 82.5 to 85.4% for multivariate LDA, with maximum mandibular body height identified as the most significant predictor (87.4%). This pilot study establishes a reliable framework for sex estimation based on mandibular parameters in pooled Asian populations, offering significant implications for forensic and bioarchaeological applications. The effectiveness of OPLS in eliminating confounding factors was highlighted, enhancing the robustness of the findings. Future research is recommended to extend these methodologies to other Asian subgroups and develop LDA models for fragmented mandibles, thereby improving the practical utility of sex estimation techniques in forensic contexts. Valuable insights into sexual dimorphism are provided, emphasizing the potential for standardized sexing protocols across diverse Asian populations, which reinforces the importance of reliable methodologies in forensic investigations.

There is minimal published experience with naratriptan during breastfeeding. If naratriptan is required by the mother of an older infant, it is not a reason to discontinue breastfeeding, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Tinnitus, a distressing condition that can significantly impair quality of life, has been associated with several medications, including triptans. This study aimed to explore the relationship between tinnitus and specific migraine treatments, focusing on triptans and calcitonin gene-related peptide (CGRP) inhibitors. Data from the FDA Adverse Event Reporting System (FAERS) through the third quarter of 2023 were analyzed to calculate proportional reporting ratios (PRR) and reporting odds ratios (ROR) for migraine treatments, specifically triptans and CGRP inhibitors. Positive tinnitus signals were identified when PRRs or RORs were greater than 2.0, the lower bound of the 95% confidence interval exceeded 1.0, and at least three cases were reported. Intra- and inter-class analyses were conducted to compare tinnitus reports among individual drugs and drug classes. Among 47,615 tinnitus-related adverse events, 345 were associated with CGRP inhibitors and 183 with triptans. Positive tinnitus signals were observed for several CGRP inhibitors, except eptinezumab and atogepant, and for all triptans except sumatriptan. Inter-class analysis revealed no significant differences between triptans and CGRP inhibitors. However, intra-class analysis identified naratriptan, almotriptan, and frovatriptan as having notable tinnitus signals among triptans, while CGRP inhibitors did not exhibit strong signals for any specific drug. Using real-world data from FAERS and pharmacovigilance methods, this study identified tinnitus signals related to migraine treatments, particularly among certain triptans. These findings provide preliminary evidence for further investigation into the relationship between migraine medications and tinnitus.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by CAG trinucleotide expansion in the androgen receptor (AR) gene. To improve the quality of in vitro cell-based assays for the evaluation of potential drug candidates for SBMA, we developed a morphology-based phenotypic analysis for a muscle cell model of SBMA that involves multiparametric morphological profiling to quantitatively assess the therapeutic effects of drugs on muscle cell phenotype. The analysis was validated using dihydrotestosterone and pioglitazone, which have been shown to exacerbate and ameliorate the pathophysiology of SBMA, respectively. Gene expression analysis revealed activation of the JNK pathway in the SBMA cells compared to the control cells. Phenotypic analysis revealed the effect of naratriptan, a JNK inhibitor, on the phenotypic changes of SBMA cells, and the results were confirmed by LDH assays. We then trained a predictive machine learning model to classify the drug responses, and it successfully discriminated between pioglitazone-type and naratriptan-type morphological profiles based on their morphological characteristics. Our morphology-based phenotypic analysis provides a noninvasive and efficient screening method to accelerate the development of therapeutics for SBMA.

Objective: Japan has resumed its health technology assessment to decide how to reduce high-cost drug prices. While drug price rules in Japan are comprehensive, they do not necessarily capture differences in product characteristics. This study examined the drug price revision strategy in Japan using migraine treatment with triptans as an example. Cost data from fiscal years (FY) 2018, 2020, and 2022 were utilized. Methods: A cost-utility analysis was conducted from the perspective of healthcare payers, focusing on Japanese patients aged over 18 years experiencing migraines. The study employed a base-case model with probabilities derived from a network meta-analysis. Direct costs included medical and drug costs. Effectiveness was assessed using the European Quality of Life 5-dimensions-3-level questionnaire. Deterministic and probabilistic sensitivity analyses were conducted to examine the level of uncertainty. Results: In FY2018, sumatriptan and eletriptan were cost-effective; however, the other triptans were dominated by sumatriptan. In FY2020, sumatriptan and eletriptan were cost-effective, and rizatriptan was extended-dominated; nevertheless, the other triptans were dominated by sumatriptan. In FY2022, naratriptan and eletriptan were cost-effective; however, the other triptans were dominated by naratriptan. The hierarchy of triptan strategies varied in each fiscal year. Conclusions: This study provides valuable insights into the drug price revision strategy in Japan. The variations could be problematic because in Japan, formulary management of triptans, for example, those for migraine, may face revaluation every other year. Discussions regarding this issue will be further explored in the future.