Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Models to evaluate the pulmonary toxicity of desert dust and what we have learned from them so far: a mini-review.","authors":"Gerrit Bredeck, Roel P F Schins","doi":"10.1007/s00210-025-03891-9","DOIUrl":"https://doi.org/10.1007/s00210-025-03891-9","url":null,"abstract":"<p><p>Millions of people worldwide are exposed to aerosolised desert dust and are at risk of the adverse respiratory health effects it causes. This mini-review gives an overview of the study types that can be used to assess the respiratory toxicity of desert dust and the insights gained from these studies. We highlight the main advantages and disadvantages of epidemiological, in vivo, and in vitro studies. Regarding in vitro studies, we discuss models of increasing complexity, i.e., traditional submerged cell cultures, air-liquid interface cultures, organ-on-a-chip models, organoids, and precision-cut lung slices. Epidemiological studies have shown increased short-term mortality and exacerbated acute and chronic respiratory diseases after desert dust events. In contrast, a connection to the onset of chronic diseases is more difficult to prove. In vivo and in vitro studies have particularly addressed the cellular and molecular effects of desert dust. It was found that desert dust activates immune cells and induces the expression of inflammatory cytokines and oxidative stress markers. The specific effects and their extent vary between dust samples from different sources. The investigation of the role of the composition is still immature and needs further effort including more extensive screenings. The advancement of easy-to-handle and realistic pulmonary in vitro models is required to automate screenings, support mechanistic insights, and enable the assessment of long-term exposure scenarios. In agreement with striving to develop new approach methodologies, such advancements can reduce and replace animal experiments and strongly benefit the translatability of research outcomes to human health protection.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743508","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":"Retraction Note: Advances in microscopy characterization techniques for lipid nanocarriers in drug delivery: a comprehensive review.","authors":"Mohamed J Saadh, Mohammed Ali Shallan, Uday Abdul-Reda Hussein, Amjed Qasim Mohammed, Saeb Jasim Al-Shuwaili, Mukaram Shikara, Ahmed Ali Ami, Noor Alhuda Mohammad Ali Khalil, Irfan Ahmad, Huda Hayder Abbas, Ahmed Elawady","doi":"10.1007/s00210-025-04104-z","DOIUrl":"https://doi.org/10.1007/s00210-025-04104-z","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742138","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":"B-AP15 inhibited colon cancer cell proliferation by decreasing CDK6, Cyclin A, Cyclin E, c-Myc, and VEGF gene expression.","authors":"Thanet Sophonnithiprasert, Sasiwan Konjanthet, Nattanicha Narinnork, Napat Prompat, Soottawat Benjakul, Jirakrit Saetang, Siriphorn Chimplee, Nadeeya Mad-Adam, Potchanapond Graidist, Thidarath Rattanaburee","doi":"10.1007/s00210-025-03940-3","DOIUrl":"https://doi.org/10.1007/s00210-025-03940-3","url":null,"abstract":"<p><p>This study evaluated the screening of novel possible target proteins of B-AP15 (NSC687852) in silico. Through in vitro investigation, the anticancer activity of B-AP15 was examined with respect to gene expression and cell proliferation of SW620 cells (colon cancer cells). Twenty proteins associated with colon cancer were selected to screen possible target proteins of B-AP15 using molecular docking. The binding position of B-AP15 and the top five candidate proteins were investigated using the Discovery Studio 2021 software program. Cytotoxicity, colonization ability, and cell inhibition were evaluated in SW620 cells for 24, 48, and 72 h via MTT assay, colony formation assay, and trypan blue assay. The gene expression was estimated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 48 h. B-AP15 showed higher binding to E2F8 (- 10.88 kcal/mol), Ras (- 10.86 kcal/mol), GSK3B (- 10.77 kcal/mol), CDK6 (- 10.75 kcal/mol), and Raf (- 10.12 kcal/mol) than to USP14 (- 7.83 kcal/mol) as a target protein of B-AP15. Interestingly, Ras, GSK3B, and CDK6 shared the binding position between B-AP15 and known inhibitors. The IC₅₀ values of B-AP15 against SW620 cells for 24, 48, and 72 h were 0.89 ± 0.0019 µM, 1.38 ± 0.16 µM, and 1.77 ± 0.0016 µM, respectively. B-AP15 reduced cell viability and the size and number of colonies and increased cell inhibition in a time- and dose-dependent manner. CDK6, Cyclin A, and VEGF expression were inhibited at B-AP15 concentrations of 0.89 and 1.78 µM after treatment for 48 h. Cyclin E and cMyc expression were suppressed only at 1.78 µM. These results suggest that B-AP15 possesses cytotoxicity, reducing the size and number of colonies and increasing cell inhibition via suppression of CDK6, Cyclin A, Cyclin E c-Myc, and VEGF.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743441","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":"Authors must follow the editorial guidelines on the use of large language models in review papers.","authors":"Roland Seifert, Erik Hartman, KeWei Wang, Daniela Yildiz","doi":"10.1007/s00210-025-04102-1","DOIUrl":"https://doi.org/10.1007/s00210-025-04102-1","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743435","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":"Role of regulatory immune cells in pathogenesis and therapy of periodontitis.","authors":"Xiao Tan, Jinsong Li","doi":"10.1007/s00210-025-04045-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04045-7","url":null,"abstract":"<p><p>Periodontitis disease (PD) is a serious gum infection that progresses from gingivitis. PD is defined by gingival recession and bone loss and can lead to tooth loss. Bacterial infections are the main cause, as they induce inflammation and the development of periodontal pockets. Traditional therapies such as scaling and root planning aim to remove the subgingival biofilm via mechanical debridement but fail to address the fundamental inflammatory imbalance within the periodontium. The immune homeostasis linked to periodontal health necessitates a regulated immuno-inflammatory response, within which the presence of regulatory cells is critical to guarantee a managed response that reduces unintended tissue damage. Given that regulatory cells influence both innate and adaptive immunity, pathological conditions that might be alleviated through the establishment of immuno-tolerance, such as PD, could potentially gain from the application of regulatory cell immunotherapy. This review will reveal regulatory cell types, how they change phenotypes, and how they can be targets for new immunotherapies. As our understanding of regulatory cell biology advances, we can create novel therapeutics to improve their stability and function in PD.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736033","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":"The effects of flavonoid baicalein on miRNA expressions in cancer: a systematic review.","authors":"Mohanna Khandan, Mohammad Amin Khazeei Tabari, Seyed Mostafa Rahimi, Mahmoud Hassani, Abouzar Bagheri","doi":"10.1007/s00210-025-04078-y","DOIUrl":"https://doi.org/10.1007/s00210-025-04078-y","url":null,"abstract":"<p><p>Baicalein from Scutellaria baicalensis influences miRNA expression in various cancers, affecting key signaling pathways (PI3K/AKT, Wnt/β-catenin, mTOR) and processes like tumor growth, apoptosis, and metastasis. miRNAs, as small non-coding RNAs, play crucial roles in the cancer pathogenesis-associated gene regulations. This study is aimed at systematically reviewing the effects of baicalein on miRNA expression in various cancers. A comprehensive systematic review was conducted following PRISMA guidelines to investigate the impact of baicalein on miRNA expression in cancer. Databases including PubMed, Scopus, and Web of Science were systematically searched using key search terms. Inclusion criteria encompassed studies reporting changes in miRNA expression following baicalein treatment in cancer cell lines and animal models. Data extraction and risk of bias assessment based on SYRCLE's risk of bias tool were performed to ensure methodological rigor and reliability of the findings. Fifteen studies meeting the inclusion criteria were included in the systematic review. Baicalein impacts miRNA expression in cancers like hepatocellular carcinoma, breast, cervical, ovarian, and gastric cancers, suggesting its potential as a multi-cancer therapeutic. Baicalein regulates tumor-related genes (HDAC10, MDM2, Bcl-2/Bax, and Cyclin E1) and signaling molecules (AKT, FOXO3α), affecting cell viability, apoptosis, and cell cycle, indicating targeted therapeutic potential. In vitro and in vivo studies show baicalein inhibits tumor growth, enhances apoptosis, and regulates cell proliferation, supporting its anticancer effects. Baicalein exhibits potential in modulating miRNA expression in cancer, offering avenues for therapeutic intervention. However, methodological rigor in future studies is essential to enhance the reliability and validity of findings. Comprehensive understanding of baicalein's effects on miRNA expression holds promise for developing novel cancer treatment strategies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736038","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":"Bioinformatics-based identification of mirdametinib as a potential therapeutic target for idiopathic pulmonary fibrosis associated with endoplasmic reticulum stress.","authors":"Junwei Chen, Yuhan Du, Qi Yu, Dongyu Liu, Jinming Zhang, Tingyue Luo, Haohua Huang, Shaoxi Cai, Hangming Dong","doi":"10.1007/s00210-025-04076-0","DOIUrl":"https://doi.org/10.1007/s00210-025-04076-0","url":null,"abstract":"<p><p>The molecular link between endoplasmic reticulum stress (ERS) and idiopathic pulmonary fibrosis (IPF) remains elusive. Our study aimed to uncover core mechanisms and new therapeutic targets for IPF. By analyzing gene expression profiles from the Gene Expression Omnibus (GEO) database, we identified 1519 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) diagnostic for IPF. Using weighted gene co-expression network analysis (WGCNA) and differential expression analysis, key genes linked to IPF were pinpointed. CIBERSORT was used to assess immune cell infiltration, while the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore biological mechanisms. In three GEO datasets (GSE150910, GSE92592, and GSE124685), the receiver operating characteristic (ROC) curve analysis showed area under the ROC curve (AUC) > 0.7 for all ERSRGs. The Connectivity Map (CMap) database was used to predict small molecules modulating IPF signatures. The molecular docking energies of mirdametinib with protein targets ranged from - 5.1643 to - 8.0154 kcal/mol, while those of linsitinib ranged from - 5.6031 to - 7.902 kcal/mol. Molecular docking and animal experiments were performed to validate the therapeutic potential of identified compounds, with mirdametinib showing specific effects in a murine bleomycin-induced pulmonary fibrosis model. In vitro experiments indicated that mirdametinib may alleviate pulmonary fibrosis by reducing ERS via the PI3K/Akt/mTOR pathway. Our findings highlight 11 ERSRGs as predictors of IPF and demonstrate the feasibility of bioinformatics in drug discovery for IPF treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735995","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":"FOXA1-mediated transcription of MFAP2 facilitates cell growth, metastasis and cisplatin resistance in uterine corpus endometrial carcinoma.","authors":"Jie Bai, Jing Bai, Hongzhen Zhang","doi":"10.1007/s00210-025-04041-x","DOIUrl":"https://doi.org/10.1007/s00210-025-04041-x","url":null,"abstract":"<p><p>Microfibril-associated protein 2 (MFAP2) has been confirmed to be an oncogene to participate in regulating the progression of many cancers. However, its role and mechanism in the development of uterine corpus endometrial carcinoma (UCEC) are still unclear. The mRNA and protein levels of MFAP2 and forkhead box A1 (FOXA1) were determined using qRT-PCR and western blot. Cell proliferation, apoptosis, migration, invasion and cisplatin resistance were detected by colony formation assay, EdU assay, flow cytometry, transwell assay and CCK8 assay. Xenograft tumor models were constructed to explore the effect of MFAP2 knockdown on UCEC tumorigenesis and cisplatin resistance in vivo. The interaction between FOXA1 and MFAP2 promoter was evaluated by ChIP assay and dual-luciferase reporter assay. MFAP2 was upregulated in UCEC tissues and cells. Silencing of MFAP2 repressed UCEC cell growth, metastasis and cisplatin resistance in vitro, as well as reduced tumorigenesis in vivo. In terms of mechanism, FOXA1 bound to MFAP2 promoter region to increase its expression. FOXA1 knockdown could inhibit UCEC cell growth, metastasis and cisplatin resistance. Moreover, FOXA1 promoted growth, metastasis and cisplatin resistance in UCEC cells via enhancing MFAP2 expression. FOXA1-activated MFAP2 might contribute to the growth, metastasis and cisplatin resistance of UCEC cells, providing a novel target for UCEC treatment.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736030","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":"Disafynol: A polyacetylene dimer from Centaurea schmidii enhancing breast cancer cell apoptosis via oxidative and ER stress pathways.","authors":"Zeinab Babaei, Mustafa Ghanadian, Mahmoud Aghaei","doi":"10.1007/s00210-025-04085-z","DOIUrl":"https://doi.org/10.1007/s00210-025-04085-z","url":null,"abstract":"<p><p>Phytochemical analysis of the aerial parts of Centaurea schmidii Wagenitz (Asteraceae) led to the isolation of disafynol, a novel polyacetylene, for the first time. This study investigated its anti-cancer effects and the mechanisms underlying these effects in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive) breast cancer cell lines. The cytotoxic effects of disafynol were evaluated using various concentrations to measure cell viability, apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), caspases-12/6 activity, and protein aggregation. Expression of apoptotic markers and endoplasmic reticulum (ER) stress-related genes was analyzed by western blot and reverse transcription-PCR analyses, respectively. Disafynol exhibited dose-dependent cytotoxicity, with greater potency in MDA-MB-231 cells (IC50: 10.6 µM) compared to MCF-7 cells (IC50: 30 µM), indicating hormone receptor-independent manner of cell growth inhibition. Treating cells with disafynol caused significant apoptosis, marked by enhanced ROS production and reduced MMP. Meanwhile, disafynol induced Bcl-2 downregulation, Bax upregulation, and caspase-12/6 activities in both breast cancer cells. Additionally, disafynol triggered ER stress, as evidenced by protein aggregation and upregulation of genes related to ER stress, including BIP, ATF4, CHOP, and XBP-1. Overall, disafynol demonstrates significant pro-apoptotic effects on breast cancer cells by inducing oxidative stress and activating the ER stress pathway. Its hormone receptor-independent cytotoxicity suggests potential therapeutic applications for treating breast cancers, including triple-negative subtypes.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736009","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":"Formulation and evaluation of polymeric nanoparticles to improve in vivo chemotherapeutic efficacy of mangiferin against breast cancer.","authors":"Pratik Chakraborty, Ananya Das, Sharmistha Chatterjee, Aparajita Bairagi, Hiranmoy Bhattacharya, Chiranjib Bhattacharyya, Nabanita Chatterjee, Parames C Sil, Saikat Dewanjee","doi":"10.1007/s00210-025-04068-0","DOIUrl":"https://doi.org/10.1007/s00210-025-04068-0","url":null,"abstract":"<p><p>Mangiferin (Mgf), a naturally occurring polyphenol, can act as an apoptosis inducer for various cancer cells. Thus, it is holding the prospect of being a promising chemotherapeutic agent. However, a discrepancy between the in vitro results and in vivo observations seems to exist that apprehends its potential usefulness. The in vivo chemotherapeutic capacity of Mgf is greatly challenged because of the unfavorable pharmacokinetic credentials. The present study aims to overcome the biopharmaceutical limitations and improve the chemotherapeutic efficacy by incorporating it within nano-scale delivery system. Stable and sphere-shaped Mgf-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (MNPs) were formulated using the nanoprecipitation method and characterized. Further, MNPs were assessed through multiple in vitro and in vivo preclinical evaluations for their chemotherapeutic efficacy, with an ambition to improve the performance in the biological system. Sphere-shaped MNPs exhibited satisfactory drug loading and release profile. The Mgf-loaded nanoformulation also exhibited better cytotoxic potential against breast cancer cells compared to native Mgf owing to its better penetrability into cancer cells. MNPs were also found to confer superior in vivo chemotherapeutic efficacy in breast cancer-bearing mice evidenced by the reduction of tumor load. Improved anti-cancer potential of MNPs over free Mgf was also established through different bioassays. Moreover, the nanoparticles did not confer systemic toxicity to levels of concern. To conclude, the current study pleads for MNPs as a safe and efficacious tool in the fight against breast cancer for futuristic translations.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736013","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}