Since the publication of the Taiwan Headache Society's 2022 Guidelines for the Acute Treatment of Migraine Attacks, advances in headache medicine and the approval of new drugs in Taiwan have necessitated an update. To address clinical needs, the Guideline Committee of the Taiwan Headache Society reviewed evidence for pharmacological and non-pharmacological acute treatments using evidence-based principles. Drawing from the latest European, American, and international guidelines, and through expert consensus, this revision updates treatment roles, grades of recommendation, efficacy, and adverse-effect profiles. Currently, a broad range of medications is available in Taiwan for acute migraine management, categorised into "specific" and "non-specific" agents. Specific treatments include oral and intranasal triptans, and gepants, i.e., oral calcitonin gene-related peptide (CGRP) receptor antagonists. Non-specific agents include acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs: diclofenac, ibuprofen, naproxen). Injectable prochlorperazine is also strongly recommended. Ergotamine/caffeine combinations are less effective and are second-line agents, while high-dose aspirin is limited by gastrointestinal risk. Considering the potential risk of dependency, tramadol or tramadol/paracetamol combinations should be reserved until all other agents fail, and should be limited to oral forms. Other opioids, such as morphine, butorphanol, etc., lack evidence and are not recommended. Treatment should follow the principle of stratified care: oral NSAIDs for mild disability, with combination analgesics or parenteral NSAIDs as alternatives, and oral or intranasal triptans for moderate to severe disability, ideally administered early. Antiemetics may be added, and combining triptans with NSAIDs enhances efficacy. Rimegepant can be considered a first-line therapy, particularly for patients who are unresponsive or intolerant to triptans, have cardiovascular contraindications, or are at risk of developing medication overuse. In status migrainosus, parenteral corticosteroids with intravenous fluids are advised. Acetaminophen remains first-line for children and pregnant women. To prevent medication-overuse headache, acute treatments, including NSAIDs, acetaminophen, triptans, ergot derivatives, and combination analgesics, should not exceed two days per week, probably with the exception of rimegepant.

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.

The combination of ergotamine and caffeine is a medication used in the management and treatment of acute migraines. It is in the ergot alkaloid class of drugs. This article outlines the indications, action, and contraindications for Ergotamine/caffeine as a valuable agent in the treatment of acute migraines. This article will highlight the mechanism of action, adverse event profile, and other key factors, including dosing, pharmacokinetics, monitoring, and relevant interactions pertinent for members of the interprofessional healthcare team in the care of patients with acute migraines and related conditions.

Candida albicans is the leading cause of vulvovaginal candidiasis (VVC), a multifactorial disease of the lower female reproductive tract. Despite numerous studies, the molecular-pathophysiology during VVC and its commensal state within the host remains elusive. To address this, we performed a comprehensive computational analysis by integrating RNA-Seq datasets from both host and pathogen. Differentially expressed genes were identified and used to construct three network models: within the pathogen, host, and host-pathogen interaction. Subsequent inter-network nodes mapping enabled us to attain two distinct condition-specific fungal targeted networks in the host, during VVC (466 nodes and 496 edges) and commensal state (162 nodes and 176 edges), which were validated by condition-specific immune response by gene ontology analysis. Intending to target pathogenesis while preserving its commensal integrity, we identified an exclusive fungal protein Zfu2p that acts as a master regulator in the gene regulatory network of the pathogen. It promotes pathogenic attributes through its target gene RNR22 and interacts with the host protein UBC. Subsequently, the drug repurposing strategy coupled with molecular dynamics analysis identified Ergotamine as a promising candidate, which may disrupt biofilm formation while preserving commensal balance. This study offers insights into VVC pathophysiology and suggests a targeted therapy, though experimental validation of Ergotamine's efficacy remains essential.

Understanding the molecular mechanisms underlying mycotoxin toxicity is crucial for risk assessment and public health protection. In this study, we performed comprehensive molecular docking analysis of 434 structurally diverse mycotoxins against a panel of 44 human protein targets associated with acute toxicity effects. Docking results revealed that 18.2% of all interactions had binding energies ≤ -9 kcal/mol. We identified which proteins across the panel were most vulnerable to mycotoxins: acetylcholinesterase, serotonin transporter, and adrenergic receptors (ADRB1 and ADRB2). Analysis identified most promiscuous mycotoxins, including β-asperlicin C and ergotamine, the latter demonstrating the most favorable predicted binding to HTR1B ([Formula: see text] kcal/mol), consistent with experimental data. Class-specific binding pattern analysis revealed that aflatoxins and ochratoxins exhibit broad multi-target activity. These findings provide systematic insights into the molecular basis of mycotoxin toxicity and identify priority targets for future experimental validation and public health monitoring strategies. The dataset containing the affinity data is publicly available at https://github.com/chemagents/mycotoxins-antitargets.

Dihydroergotamine (DHE) was first approved in 1946 for the acute treatment of migraine. Its efficacy when administered as an intravenous (IV) injection explains its enduring use in the management of migraine today. More recently, attention has been focused on the development of formulations delivered by the inhalational route to either the nasal mucosa or lung with the objective of providing a product that enables easy, needle-free, "at-home" use that is rapidly effective. Three new DHE products for migraine (two administered by nasal delivery) have been Food and Drug Administration (FDA) approved in the past five years with two others using pulmonary delivery in clinical development attempting to optimize outcomes for subjects requiring "at-home" migraine treatment. This narrative review describes those DHE development programs, and others that have failed, with the objective of providing a broad perspective on various approaches, including those that may be more likely to achieve the goals of high efficacy rates, rapid relief, and convenience of use. In addition, DHE has been investigated for potential repurposing of other indications. These too are described.

Migraine is the most prevalent neurological condition, which affects 1.16 million individuals globally, ranking first among adolescents and children and second in the case of adults aged under 60 years. Both genetic and environmental factors contribute to its pathophysiology, influencing treatment outcomes and drug responses. Pharmacogenomics has emerged as a critical field in understanding interindividual variability in migraine therapy. Genetic variants in pharmacokinetic and pharmacodynamic pathways impact the metabolism, efficacy, and adverse drug reactions of drugs used in migraine. Variants in genes such as PLCE1, SRP72, CACNA1D, and CACNA1C affect calcium channel blockers' efficacy, while polymorphisms in GNB3 and DRD2 influence triptan response. CYP3A4 and CYP2D6 polymorphisms influence the metabolism of ergot alkaloids and beta blockers, impacting their efficacy and toxicity. The TSPAN2 gene is associated with reduced ergotamine response in patients with migraines without aura. Moreover, CGRP receptor antagonists exhibit varying effectiveness based on the receptor gene variants. This review compiles current pharmacogenetic insights to optimize migraine treatment through personalized medicine. Understanding these genetic markers could lead to improved therapeutic strategies, reducing trial-anderror prescribing and improving patient outcomes. Further research is warranted to verify these associations and translate outcomes into clinical practice.

Postoperative delirium (POD) is clinically associated with a variety of adverse outcomes. The incidence of POD in patients undergoing radical resection of lung cancer is about 5% to 16%, higher than that in patients undergoing other surgeries. However, the molecular mechanisms that specifically lead to POD after radical resection of lung cancer have not been fully elucidated. Gene expression profile datasets of lung cancer (GSE31210) and POD (GSE163943) were downloaded from the Gene Expression Omnibus database. The weighted gene co-expression network analysis (WGCNA) was used to screen key model genes. Differentially expressed genes between disease and control groups were selected. Function enrichment analysis was applied to reveal various biological processes of genes. The hub factors were further selected by protein-protein interaction network, and potential therapeutic drugs were screened using molecular docking. A total of 28 differentially expressed co-expression key module genes shared by lung cancer and POD were obtained. These genes were involved in Fanconi anemia pathway, glycosaminoglycan degradation, and pentose phosphate pathway. A predicted protein-protein interaction network was constructed, which contained 7 proteins. CDC20 (cell division cycle protein 20) had a higher degree. Molecular docking revealed that the drug ergotamine had the lowest docking binding energy with the target protein. Fanconi anemia pathway, glycosaminoglycan degradation and pentose phosphate pathway may play a key role in the pathogenesis of POD after lung cancer surgery via. Ergotamine may serve as a candidate drug for lung cancer-related POD.

Phosphorylation of serine residues within SQ/TQ motifs, particularly Ser237 of the ATP-dependent DNA helicase DDX11, by ataxia telangiectasia mutated (ATM) kinase plays a key role in activating the DNA damage response (DDR) in liver cancer. To disrupt this signaling pathway, we applied a computationally guided drug repurposing approach to identify FDA-approved compounds capable of targeting critical DDX11 residues. A library of 2367 drugs was screened using a structure-based, site-specific docking strategy, yielding seven candidates with binding affinities from -6.5 to -7.7 kcal/mol. Although Afatinib showed the strongest docking score (-7.674 kcal/mol), it lacked hydrogen-bond interactions with Ser237 and Gln238 and was therefore excluded. In contrast, dacomitinib, ergotamine, and cabozantinib displayed both favorable affinities and stable hydrogen-bonding with these key residues. Comprehensive molecular dynamics simulations (100 ns) confirmed the conformational stability of the selected complexes, while MM-GBSA/MM-PBSA and principal component analyses supported strong and persistent binding. Among them, cabozantinib was prioritized for experimental validation due to its clinical relevance in hepatocellular carcinoma and selective interaction with Ser237. Proteomic profiling further revealed that cabozantinib downregulates DNA repair proteins and attenuates homologous recombination (HR) repair capacity in liver cancer cells. Together, computational and experimental findings indicate that targeting DDX11, particularly at Ser237, may effectively suppress ATM-mediated DDR signaling and impede liver cancer progression, warranting further preclinical and clinical evaluation.

BACKGROUND: The association between smoking and cluster headache (CH) has been consistently documented, with high rates of tobacco exposure observed among CH patients and several studies reporting links between smoking status and differences in disease onset, clinical features, and treatment response. However, the biological basis of this association remains uncertain, and no causal relationship has been established. To better characterize this interaction, the present study investigates the relationship between smoking and CH using three complementary analytical approaches. METHODS: In this multicenter study, participants with confirmed CH diagnosis completed a comprehensive survey addressing smoking habits, clinical features, and treatment responses. The study employed three analytical approaches: comparing smokers versus non-smokers, examining gender differences among smokers, and performing cluster analysis to identify distinct patient subgroups. RESULTS: Among 318 participants (76.7% male), 78.6% were smokers (current or former). Smokers reported higher rates of autonomic symptoms and suicidal thoughts compared to non-smokers. Non-smokers demonstrated better response to oral triptans and ergotamine, while subcutaneous sumatriptan was more effective in smokers. Female smokers experienced longer attack durations, while male smokers showed better triptan responsiveness. Cluster analysis revealed two groups: Cluster 2 comprised predominantly smokers (85.7%), showed earlier disease onset, and experienced more intense autonomic symptoms and attack-associated features compared to Cluster 1. CONCLUSIONS: This study identifies differences in treatment response profiles between smokers and non-smokers, gender-related variations, and distinct clinical patterns associated with smoking status in patients with CH. These findings point to the potential value of considering smoking status when characterizing CH subgroups and designing individualized management strategies. However, as this is an observational study, the associations reported here should not be interpreted as evidence of causality, and further prospective and mechanistic research is required to clarify the nature of these relationships.