Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Integrative single-cell transcriptomics and co-expression network analysis identify SIMALR as a prognostic immune-related lncRNA in breast cancer: in silico analysis and validation.","authors":"Fatemeh Balangi, Pouria Samadi, Fatemeh Maghool, Hamid Daneshvar, Maryam Tabatabaeian, Elham Amjadi, Farnaz Sedghy","doi":"10.1007/s00210-026-05156-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05156-5","url":null,"abstract":"<p><p>This study aimed to identify and characterize irlncRNAs associated with prognosis and immune modulation in breast cancer. We integrated single-cell RNA sequencing, hdWGCNA, and bulk RNA-seq differential expression analysis results to identify candidate irlncRNAs. The top candidate, SIMALR, was further investigated using immune, survival, mutation analysis, and GSEA. RT-qPCR preliminary validation was performed on patient tissues. SIMALR was linked to favorable survival and enriched in immune pathways, including T-cell receptor signaling, Natural Killer (NK) cell cytotoxicity, and antigen processing. Pearson analysis showed co-expression of SIMALR-related genes (CD8A, CD4, TNF, LCP2, ITGB2) in key immune populations. High SIMALR As per standard instruction, \"Statement of Significance\" section should not be captured. Hence, the \"Clinical significance\" section was deleted. Please check and confirm if presented correctly; otherwise, please amend. expression in tumor cells is associated with enhanced secretion of Th1-attracting chemokines (CXCL9/10/11, CCL5), recruitment of CD8 + T cells, activated dendritic cells, and both M1/M2 macrophages. RT-qPCR confirmed higher SIMALR expression in tumors. Due to limited availability of clinical specimens, the RT-qPCR analysis was performed on paired tissue samples from six patients, and therefore the results should be considered a preliminary validation. SIMALR may contribute to anti-tumor immunity, highlighting its potential as a promising biomarker and therapeutic target in breast cancer.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: New drugs and their performance 10 years after approval: a systematic analysis.","authors":"Bores Manfouo, Roland Seifert","doi":"10.1007/s00210-026-05372-z","DOIUrl":"https://doi.org/10.1007/s00210-026-05372-z","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Cardioprotective effects of notoginsenoside R1 on myocardial remodeling and cardiac function in restraint stress‑induced MI in rats.","authors":"Peng Sun, Cuiyu Han, Qian Sun, Tingting Li, Lan Li, Mingxing Shi, Pei Zhao, Lu Chen, Na Li","doi":"10.1007/s00210-026-05393-8","DOIUrl":"https://doi.org/10.1007/s00210-026-05393-8","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.","authors":"Pooja Singh, Shreya Sridhar, Dwarithaa Balasubramanian, Devi Maigandan, Harish Chinnakonda Chandramoorthy, Trivadi Ganesan, Rajesh Kumar Gandhirajan","doi":"10.1007/s00210-026-05320-x","DOIUrl":"https://doi.org/10.1007/s00210-026-05320-x","url":null,"abstract":"<p><p>Reactive oxygen and nitrogen species (RONS) constitute a unifying molecular axis across various cancer therapy modalities and are primary regulators of regulated cell death (RCD). Generally, cancer cells function under high oxidative stress to maintain proliferation, making them vulnerable to therapeutic approaches that push RONS levels above their survival threshold. The purpose of this review is to consolidate mechanistic evidence linking redox modulation to therapeutic efficacy. We analyzed current literature regarding standard and emerging anticancer modalities, including radiotherapy, proton therapy, FLASH therapy, chemotherapy, cold atmospheric plasma, photodynamic therapy, and engineered nanoplatforms. We specifically examined the molecular mechanisms by which these therapies induce mitochondrial ROS accumulation and trigger distinct cell death pathways. Our literature review indicates that these diverse modalities achieve tumor selectivity by increasing mitochondrial ROS beyond cytotoxic limits. When combined strategically, they further promote tumor-specific oxidative stress, maximizing therapeutic efficacy while minimizing damage to healthy tissues. We also highlight the critical biosafety considerations and regulatory frameworks necessary for the safe clinical translation of these RONS-based treatments. Redox-modulating strategies can address critical challenges, including chemoradiation resistance, metabolic rewiring, and the persistence of cancer stem cells. We propose that RONS-centered therapeutic design represents a viable strategy to improve the efficacy of contemporary cancer treatments by combining redox biology with cutting-edge therapeutic engineering. This graphical abstract depicts how various cancer treatment modalities cause RONS-mediated oxidative stress, hence activating different cell death pathways in cancer cells.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer multi-omics analysis identifies TOMM22 as an oncogenic driver and therapeutic target in LIHC via ferroptosis regulation.","authors":"Wei Cheng, Chengdan Meng, Min Chen","doi":"10.1007/s00210-026-05400-y","DOIUrl":"https://doi.org/10.1007/s00210-026-05400-y","url":null,"abstract":"<p><p>Mitochondrial dysfunction plays a pivotal role in tumor progression. TOMM22, a core receptor of the mitochondrial protein import complex, has been implicated in various cancers, though its pan-cancer roles remain insufficiently defined. This study aimed to explore the pan-cancer profile of TOMM22 and investigate its function in hepatocellular carcinoma (LIHC). We utilized multiple bioinformatics platforms to perform pan-cancer analyses of TOMM22 expression, prognostic value, mutations, and immune infiltration. Transcriptomic, single-cell, and spatial transcriptomic data from LIHC were used to validate TOMM22 expression and its clinical significance. In vitro experiments were conducted to examine its biological functions in LIHC cells. TOMM22 was significantly overexpressed in multiple cancer types, including LIHC, where it was associated with poor prognosis and high diagnostic value. Mutations in TOMM22 were linked to impaired survival outcomes, and its expression correlated with immune infiltration, cancer stemness, and mitochondrial function. In LIHC, TOMM22 upregulation was associated with advanced tumor grade and resistance to sorafenib. Knockdown of TOMM22 inhibited LIHC cell proliferation and induced ferroptosis by accumulating lipid reactive oxygen species (ROS) and promoting lipid peroxidation. This study provides comprehensive insights into the oncogenic role of TOMM22 across cancers, identifying it as a promising diagnostic biomarker and therapeutic target for the precision treatment of LIHC.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib-induced Sweet syndrome.","authors":"Noor Almaani, Zain Al Ta'ani, Maram Abdaljaleel, Faris AlShammas, Alaa Alshorman","doi":"10.1007/s00210-026-05399-2","DOIUrl":"https://doi.org/10.1007/s00210-026-05399-2","url":null,"abstract":"<p><p>Ibrutinib is an oral targeted drug that has been approved by the US Food and Drug Administration (FDA) for the management of chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia, and previously treated chronic graft-versus-host disease. It is an irreversible selective inhibitor of Bruton's tyrosine kinase (Btk)1. We report the case of a 54-year-old male patient, diagnosed with CLL being who was with ibrutinib. He developed several erythematous and indurated plaques on the neck, face, hands, and scalp, 8 months into his treatment. Clinical features along with skin biopsy findings of a neutrophil predominant infiltrate were consistent with the diagnosis of Sweet syndrome. Upon withdrawal of the medication and application of a potent topical steroid, cutaneous lesions healed after one week. However, readministration of the medication at a lower dose was associated, with recurrence of the lesions, suggesting a temporal relationship with ibrutinib and necessitating drug discontinuation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic potential of autochthonous Enterobacter mori ASP8 and Bacillus stercoris ASP10 isolated from gut microbiota of healthy stinging catfish, Heteropneustes fossilis (Bloch).","authors":"Pritish Mitra, Somen Dey, Arindam Ganguly, Sabyasachi Chatterjee, Asish Mandal","doi":"10.1007/s00210-026-05360-3","DOIUrl":"https://doi.org/10.1007/s00210-026-05360-3","url":null,"abstract":"<p><p>This study characterizes two bacterial isolates Enterobacter mori ASP8 and Bacillus stercoris ASP10, derived from the stinging catfish (Heteropneustes fossilis) and evaluates in vitro probiotic efficacy for enhancing sustainability in freshwater aquaculture. Rigorous biosafety assessments confirmed that both strains were non-hemolytic, were non-blood coagulant, lack DNase/RNase activity, and were non-biogenic amine producers. Both isolates exhibited high gastrointestinal resilience and survival under stimulated stomach duodenum passage (SSDP) with a value of 81.98% for E. mori ASP8 and 84.89% for B. stercoris ASP10. The isolates also showed strong tolerance to bile, phenol, and lysozyme. Functional assays revealed robust hydrocarbon adherence up to 84.83% and significant co-aggregation with fish pathogens varied between 50.5 and 72.69%. Notably, it was found that B. stercoris ASP10 exhibited biofilm-forming capabilities on Congo red agar. E. mori ASP8 and B. stercoris ASP10 showed strong antibacterial activity against seven pathogens by producing bacteriocin, siderophore production. In addition, the isolates exhibited cholesterol lowering, antioxidant potentially and multi-enzymatic (amylase, protease, cellulase, and lipase) activities. Overall findings concluded both strains are effective, but B. stercoris ASP10 emerged as superior probiotic candidate for future aquaculture application.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent neuropsychiatric and systemic toxicity profiles of abemaciclib and palbociclib: a triangulation study integrating pharmacovigilance, genetic epidemiology, and multi-omics profiling.","authors":"Zijian Zhang, Yue Yang, Xiaojing Li, Chengwei Cui, Yuan Fang, Chenxin Zhang, Yao Xiao, Shaochun Liu, Li Song, Chengyuan Fang, Fucheng Zhou","doi":"10.1007/s00210-026-05366-x","DOIUrl":"https://doi.org/10.1007/s00210-026-05366-x","url":null,"abstract":"<p><p>Cyclin-dependent kinase 4/6 inhibitors improve outcomes in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, but their toxicity profiles may differ in clinically meaningful ways. We aimed to compare the neuropsychiatric and systemic toxicity patterns of abemaciclib and palbociclib and to explore pharmacokinetic and molecular features that might contribute to these differences. We conducted a triangulation study integrating pharmacovigilance, Mendelian randomization, explainable machine learning, transcriptomics, and molecular docking. We analyzed 15,215 reports from the US Food and Drug Administration Adverse Event Reporting System and retained 5524 matched patients after propensity score matching. In the matched cohort, abemaciclib showed a toxicity profile more consistent with central nervous system involvement, with reporting enrichment for headache, dizziness, and memory impairment, and a shorter median time to onset than palbociclib (27.5 days vs 37.0 days). By contrast, palbociclib showed a greater reporting burden of fatigue and anxiety and a higher fatal outcome reporting rate than abemaciclib (12.46% vs 6.52%). Mendelian randomisation showed an association between genetically predicted lower CDK6 levels and reduced cognitive performance (odds ratio 0.991, 95% CI 0.983-1.000; p=0.040), but no association with C-reactive protein (odds ratio 0.999, 95% CI 0.987-1.012; p=0.914). The machine learning model achieved an area under the curve of 0.641 for prediction of central nervous system toxicity. Transcriptomic analysis showed broader transcriptional reprogramming with abemaciclib than with palbociclib, with 5450 versus 265 differentially expressed genes, while docking analysis identified more favorable predicted binding of abemaciclib than palbociclib to GSK-3β and ABCB1 in this in silico setting, providing structural support for but not proving the proposed mechanistic interpretation. Abemaciclib and palbociclib were associated with distinct neuropsychiatric and systemic toxicity patterns. These findings argue against a uniform class effect and support further prospective evaluation of drug-specific survivorship toxicity profiles.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicity evaluation of ultra-diluted methotrexate (12c and 30c): an acute and subacute oral toxicity study in animals.","authors":"Pranjal Gujarathi, Rashmi Korat, Piyush Gujarathi","doi":"10.1007/s00210-026-05328-3","DOIUrl":"https://doi.org/10.1007/s00210-026-05328-3","url":null,"abstract":"<p><p>Autoimmune diseases exhibit active and remission phases. Tissues may retain an 'inflammatory memory', increasing relapse risk after stopping treatment, necessitating ongoing therapy following remission induction. Understanding inflammatory memory and remission-to-recurrence transitions could guide strategies for achieving lasting remission while minimising long-term medication use and costs. Integrative approaches may address autoimmune conditions' multifaceted pathophysiology. Literature suggests utilising modern medicine in ultra-diluted form, with chemotherapy drugs like methotrexate undergoing ultra-dilution. However, extreme dilutions may increase toxicity due to nanoparticles' larger surface area. This study evaluated methotrexate's toxicity at 12c and 30c dilutions. An acute toxicity study evaluated single-dose effects of methotrexate 12c and 30c (2000 μL/kg) in female mice over 14 days, per OECD 423 guidelines. A repeated dose study investigated the impacts of methotrexate 12c and 30c (200 μL/kg) on male and female mice, following OECD 407 protocol. Mortality, clinical signs, body weight, haematology, biochemistry, and histopathology were comprehensively assessed. The acute toxicity study showed no animal fatalities with methotrexate, indicating the median lethal dose exceeded 2000 μL/kg. In the subacute study, methotrexate at 12c and 30c caused no mortality, adverse effects, or abnormal weight changes. Evaluations of haematological parameters, biochemical markers, and histopathological analyses of vital organs revealed no abnormalities. The research study indicates that the oral administration of methotrexate at 12c and 30c to mice over an extended duration, with a dosage of 200 μL/kg, did not exhibit any signs of toxicity or adverse reactions, thus suggesting a safe profile for these potencies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupeol as a modulator of bacterial resistance mediated by the MepA efflux pump in Staphylococcus aureus.","authors":"Nara Juliana Santos Araújo, Camila Aparecida Pereira Silva, Cicera Datiane Morais Oliveira-Tintino, Gabriel Gonçalves Alencar, Maria do Socorro Costa, Ana Raquel Pereira da Silva, Juliete Bezerra Soares, Janaína Esmeraldo Rocha, Saulo Relison Tintino, Vanessa Lima-Bezerra, Henrique Douglas Melo Coutinho, Vanessa Leopoldino Coelho Rodrigues, José Maria Barbosa-Filho, José Bezerra de Araújo-Neto, Ana Carolina Ferreira Araujo, João Arthur de Oliveira Borges, Gildênia Alves de Araújo, José Thyálisson da Costa Silva, Jacqueline Cosmo Andrade-Pinheiro","doi":"10.1007/s00210-026-05342-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05342-5","url":null,"abstract":"<p><p>Bacterial resistance constitutes one of the main threats to global public health, driving the search for therapeutic strategies capable of restoring the effectiveness of antimicrobials. Among the mechanisms involved, efflux pumps stand out, reducing the intracellular concentration of drugs and contributing to multidrug resistance. In this context, inhibitors of these pumps emerge as a promising approach, as they increase the intracellular concentration of antibiotics. Natural compounds, such as the triterpene lupeol, have been investigated as potential modulators of bacterial resistance due to their relevant biological activities. This study evaluated, from a mechanistic perspective, the ability of lupeol to inhibit the MepA efflux pump in the K2068 strain of Staphylococcus aureus. The minimum inhibitory concentration (MIC) was determined, efflux inhibition assays were performed, membrane permeability analysis was conducted using Sytox Green, ethidium bromide fluorescence was evaluated, RT-qPCR was performed, and molecular docking was performed. The results demonstrated that lupeol exhibits isolated antibacterial activity considered without clinical relevance (MIC ≥ 1024 µg/mL); however, it reduced the MIC of ciprofloxacin and ethidium bromide, indicating inhibition of the MepA pump. No alteration in membrane permeability and an increase in ethidium bromide fluorescence were observed with increasing lupeol concentration. RT-qPCR showed inhibition of mepA gene expression. In molecular docking, the compound presented a binding energy of - 9.01 kcal/mol, with van der Waals, hydrophobic, and hydrogen bonding interactions. It is concluded that lupeol shows potential as an efflux pump inhibitor, acting on the functional inhibition of the pump and the negative regulation of mepA gene expression, thus configuring itself as an adjuvant strategy in combating bacterial resistance.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}