Naunyn-Schmiedeberg's archives of pharmacology最新文献_第6页

Association between vitamin D deficiency and depressive symptoms among shift workers: Insights from network pharmacology and bioinformatics studies. 轮班工作者维生素D缺乏与抑郁症状之间的关系：来自网络药理学和生物信息学研究的见解

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-13 DOI: 10.1007/s00210-025-04709-4

Shrouq E Alrashidi, Wejdan F Alanazi, Obaid Afzal, Mubarak A Alamri

{"title":"Association between vitamin D deficiency and depressive symptoms among shift workers: Insights from network pharmacology and bioinformatics studies.","authors":"Shrouq E Alrashidi, Wejdan F Alanazi, Obaid Afzal, Mubarak A Alamri","doi":"10.1007/s00210-025-04709-4","DOIUrl":"https://doi.org/10.1007/s00210-025-04709-4","url":null,"abstract":"Vitamin D deficiency is soaring among shift workers due to multiple issues, including poor UVB experience. The objective of this study was to identify precise mechanisms by which vitamin D deficiency might aggravate depressive symptoms among shift workers. Shift work is also associated with disrupting circadian rhythm, leading to depressive symptoms. Differential expressed genes (DEGs) in depression patients (GSE80655, GSE169459, GSE217811, GSE190518, GSE98793, GSE23848, GSE76826, GSE101521, and GSE54572) and in shift workers (GSE122541) with controls were examined in the GEO database. Genes associated with vitamin D deficiency were gathered from the GenCard database. Overlapping core targets were collected by uploading genes into the Bioinformatics and Evolutionary Genomics database. STRING database was used to screen the PPI (protein-protein interaction) network of cross-targets. Cytoscape was used to select core targets and to set up the pathway-gene network. GO (Gene Ontology) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway investigations were executed by the database ShinyGO. A molecular docking examination was performed to explain the interaction between protein targets and calcitriol (active form of vitamin D), and binding affinity was confirmed by a 100-ns molecular dynamics simulation study. Our finding designated that the deficit of vitamin D might be involved in the pathology of depression among shift workers mainly through activation of the inflammatory response via upregulation of TNF, IL-6, and IL-1β (pro-inflammatory markers).","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280815","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}

引用次数: 0

The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells. SGLT2抑制剂恩格列净促进骨骼肌细胞中脂肪酸氧化的增加。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-13 DOI: 10.1007/s00210-025-04670-2

Stanislava Stevanovic, Parmeshwar B Katare, Hilde Mari Volledal, Hege G Bakke, Klemen Dolinar, Sergej Pirkmajer, D Margriet Ouwens, G Hege Thoresen, Eili T Kase, Arild C Rustan

{"title":"The SGLT2 inhibitor empagliflozin promotes increased fatty acid oxidation in skeletal muscle cells.","authors":"Stanislava Stevanovic, Parmeshwar B Katare, Hilde Mari Volledal, Hege G Bakke, Klemen Dolinar, Sergej Pirkmajer, D Margriet Ouwens, G Hege Thoresen, Eili T Kase, Arild C Rustan","doi":"10.1007/s00210-025-04670-2","DOIUrl":"https://doi.org/10.1007/s00210-025-04670-2","url":null,"abstract":"In this study we investigated the potential for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) to modify energy metabolism in human primary skeletal muscle cells and mouse C2C12 skeletal muscle cells. The results showed that treatment of human myotubes with EMPA for 96 h decreased oxidation of exogenously added glucose and acetoacetate measured as CO2 production, whereas CO2 production from exogenously added fatty acids and leucine was increased compared to control cells. Uptake of acetoacetate by the cells was decreased by EMPA. Moreover, there were no EMPA-induced changes in glucose, fatty acid or leucine uptake by human myotubes, neither was lactate concentration in cell culture medium changed after exposure to EMPA. Treatment with EMPA increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in human myotubes, while there was no effect of EMPA in human myotubes on gene expression of selected metabolic genes. Real time cell metabolic analysis in C2C12 cells showed that EMPA reduced basal respiration and glycolysis, while under conditions promoting use of endogenous fatty acids, maximal respiration and ATP production was increased by EMPA. In summary, treatment of skeletal muscle cells in vitro with EMPA caused changes in energy metabolism promoting enhanced fatty acid and leucine catabolism, decreased metabolism of glucose and acetoacetate, and reduced glycolysis. The observed changes in energy metabolism may be related to AMPK activation.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280741","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}

引用次数: 0

Protective effect of thymoquinone against acrylamide-induced hepatotoxicity in the rat: role of MAPK and apoptosis pathways. 百里醌对丙烯酰胺诱导大鼠肝毒性的保护作用：MAPK和凋亡通路的作用。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-11 DOI: 10.1007/s00210-025-04686-8

Shirin Ghasemian, Soghra Mehri, Jamshid Tabeshpour, Mohammad Reza Zirak, Fatemeh Nezhadhosein, Hossein Hosseinzadeh

{"title":"Protective effect of thymoquinone against acrylamide-induced hepatotoxicity in the rat: role of MAPK and apoptosis pathways.","authors":"Shirin Ghasemian, Soghra Mehri, Jamshid Tabeshpour, Mohammad Reza Zirak, Fatemeh Nezhadhosein, Hossein Hosseinzadeh","doi":"10.1007/s00210-025-04686-8","DOIUrl":"https://doi.org/10.1007/s00210-025-04686-8","url":null,"abstract":"Acrylamide (ACR) is widely used in industry and induces hepatotoxicity. Thymoquinone (TQ), the main constituent of the black seed (Nigella sativa L.) oil, possesses potent antioxidant and anti-apoptotic properties. The potential protective effect of TQ in ACR-induced hepatotoxicity through MAPK signaling and intrinsic/extrinsic apoptosis pathways was investigated. Animals were randomly divided into seven groups (n = 6). Control (normal saline), ACR (50 mg/kg), ACR + TQ (2.5, 5 and 10 mg/kg), ACR + vitamin E (200 mg/kg), and TQ (10 mg/kg) were administered intraperitoneally to male Wistar rats for 11 days. The content of malondialdehyde and glutathione in the liver, alanine aminotransferase, aspartate transaminase, albumin, and total serum protein were measured. Apoptosis- and mitogen-activated protein kinases (MAPK) pathway proteins in the liver were evaluated by western blotting. ACR increased AST (p < 0.001) and MDA (p < 0.01) levels and decreased GSH (p < 0.01) content in comparison to the control group. The levels of apoptosis pathway proteins (caspases 3, 8, and 9) and MAPK pathway proteins (p-p38, p-JNK, and JNK) were significantly increased in the ACR group. Co-administration of TQ (10 mg/kg) with ACR remarkably reduced AST (p < 0.01), enhanced GSH content (p < 0.001), reduced MDA level (p < 0.05), and down-regulated caspases 3, 8, and 9 (p < 0.05) and p-p38, p-JNK, and JNK proteins. ACR induces hepatotoxicity via oxidative stress and activation of MAPK and apoptosis pathways. TQ exerts a hepatoprotective effect through its antioxidant, anti-apoptotic, and MAPK-modulating properties.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275373","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}

引用次数: 0

Protective effect of trans-sodium crocetinate on nephrotoxicity induced by cisplatin: in vitro and in vivo models. 西红花酸反式钠对顺铂肾毒性的保护作用：体外和体内模型。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-11 DOI: 10.1007/s00210-025-04633-7

Danial Esmaeilzadeh, Mohammad Shariati Rad, Majid Keshavarzi, Homa Fazeli Kakhki, Hossein Hosseinzadeh, Abolfazl Khajavi Rad, Sakineh Amoueian, Bibi Marjan Razavi

{"title":"Protective effect of trans-sodium crocetinate on nephrotoxicity induced by cisplatin: in vitro and in vivo models.","authors":"Danial Esmaeilzadeh, Mohammad Shariati Rad, Majid Keshavarzi, Homa Fazeli Kakhki, Hossein Hosseinzadeh, Abolfazl Khajavi Rad, Sakineh Amoueian, Bibi Marjan Razavi","doi":"10.1007/s00210-025-04633-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04633-7","url":null,"abstract":"Trans-sodium crocetinate (TSC), a novel derivative of crocetin, has demonstrated potential protective effects against oxidative stress and apoptosis. This study aims to investigate the protective effect of TSC against cisplatin-induced nephrotoxicity by evaluating both in vivo and in vitro models. In the in vivo model, rats were pretreated with TSC (2.5, 5, and 10 mg/kg) for 5 days. Cisplatin (20 mg/kg) was injected on the 5th day to induce nephrotoxicity followed by TSC administration for an additional 2 days. Blood urea nitrogen (BUN) and serum creatinine (sCr) levels were measured to assess kidney function. Histopathological examinations and assessment of oxidative stress were conducted to evaluate renal tissue injury. In the in vitro model, HEK-293 cells were treated with cisplatin (150 µM) both with and without TSC pretreatment. Cell viability, reactive oxygen species (ROS) production, and apoptosis were subsequently evaluated. TSC significantly reduced BUN and sCr levels in rats exposed to cisplatin. Histopathological analysis revealed a reduction in tubular necrosis and other pathological changes associated with cisplatin toxicity. TSC also decreased MDA levels and increased GSH content in renal tissue. In HEK-293 cells, TSC pretreatment enhanced cell viability, reduced ROS production, and suppressed apoptosis by decreasing the Bax/Bcl-2 ratio and the expression of caspase-3 protein. TSC effectively protects against cisplatin-induced nephrotoxicity and cytotoxicity by reducing oxidative stress and apoptosis. These findings highlight TSC's potential as a therapeutic agent to mitigate the nephrotoxic effects of cisplatin in clinical settings.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275376","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}

引用次数: 0

Polyphenol-based therapeutics for glioblastoma: validation from In-vitro cell viability assay and integrated onco-omics computational analysis. 以多酚为基础的胶质母细胞瘤治疗方法：体外细胞活力测定和综合肿瘤组学计算分析验证。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-11 DOI: 10.1007/s00210-025-04690-y

Yogesh H S, Sadik Shaik, Sibghatullah Muhammad Ali Sangi, Krishna Swaroop, Sreeharsha Nagaraja, Anitha K N, Vipin Kumar Mishra, Santosh Prasad Chaudhary Kurmi, Subrata Nath, Shankar Thapa

{"title":"Polyphenol-based therapeutics for glioblastoma: validation from In-vitro cell viability assay and integrated onco-omics computational analysis.","authors":"Yogesh H S, Sadik Shaik, Sibghatullah Muhammad Ali Sangi, Krishna Swaroop, Sreeharsha Nagaraja, Anitha K N, Vipin Kumar Mishra, Santosh Prasad Chaudhary Kurmi, Subrata Nath, Shankar Thapa","doi":"10.1007/s00210-025-04690-y","DOIUrl":"https://doi.org/10.1007/s00210-025-04690-y","url":null,"abstract":"Glioblastoma (GBM) is one of the most aggressive brain tumors, with poor therapeutic outcomes due to its complex molecular profile. This study investigated the multi-target potential of three natural polyphenols-Ferulic acid, Morin, and Mangiferin-through an integrative computational strategy combining network pharmacology, onco-omics, molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT). Cross-referencing polyphenol-associated targets with GBM-related genes identified 13 common targets (e.g., PTGS2, EGFR, ESR1, MMP9). Protein-protein interaction analysis showed significant connectivity (p = 1.54 × 10⁻8), highlighting their relevance in GBM. Gene Ontology and KEGG enrichment revealed roles in proliferation, apoptosis, and migration, with enrichment in PI3K-Akt and MAPK signaling pathways. Molecular docking confirmed stable binding, with Mangiferin showing the strongest affinities: -11.0 kcal/mol (6ESM), -8.2 kcal/mol (5UGC), -7.5 kcal/mol (5UFW), and -9.1 kcal/mol (5IKT). MD simulations revealed the 5IKT-Mangiferin complex to be the most stable, with a favorable binding free energy (-32.0 ± 4.4 kcal/mol), while PCA and free energy landscapes supported reduced conformational variability. DFT results further supported favorable electronic properties. In vitro assays showed dose-dependent cytotoxicity, with IC50 values of 9.43 µM (Morin), 4.65 µM (Mangiferin), and 6.22 µM (5-FU). Collectively, Mangiferin emerged as the lead candidate with superior binding stability and multi-target potential against GBM. This integrated framework provides mechanistic insights supporting polyphenol-based therapeutic development and warrants further in vivo validation.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275354","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}

引用次数: 0

Venous thromboembolism events associated with tofacitinib in rheumatoid arthritis patients: a real-world study from FAERS database. 类风湿关节炎患者与托法替尼相关的静脉血栓栓塞事件：来自FAERS数据库的真实世界研究。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-11 DOI: 10.1007/s00210-025-04642-6

Jintuo Zhou, Ruihong Cai, Peiguang Niu, Tingting Chen, Guimu Guo, Xiaoping Zeng, Jinhua Zhang

{"title":"Venous thromboembolism events associated with tofacitinib in rheumatoid arthritis patients: a real-world study from FAERS database.","authors":"Jintuo Zhou, Ruihong Cai, Peiguang Niu, Tingting Chen, Guimu Guo, Xiaoping Zeng, Jinhua Zhang","doi":"10.1007/s00210-025-04642-6","DOIUrl":"https://doi.org/10.1007/s00210-025-04642-6","url":null,"abstract":"Tofacitinib, a Janus kinase (JAK) inhibitor approved in 2012, has become a pivotal oral treatment for rheumatoid arthritis (RA). However, the risk of venous thromboembolism (VTE) with tofacitinib in RA patients remains uncertain. This study aims to assess the association between tofacitinib use and the risk of VTE events in patients with RA using data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Additionally, this analysis sought to compare the reporting odds ratio (ROR) of VTE associated with tofacitinib and tumor necrosis factor inhibitors (TNFi). We conducted a retrospective pharmacovigilance study using FAERS data from the first quarter of 2012 to the fourth quarter of 2024. Disproportionality analysis was performed using ROR to evaluate the reporting risk of VTE events associated with tofacitinib compared with TNFi agents. A total of 1,786,456 adverse event reports related to RA were identified. Among these, 635 VTE events were associated with tofacitinib use and 1,354 VTE events were associated with TNFi agents. Tofacitinib was associated with a significantly elevated risk of VTE compared with the overall FAERS database (ROR 1.56, 95% CI 1.43-1.70) and with TNFi (ROR 2.20, 95% CI 2.00-2.40). Subgroup analysis revealed that the increased risk was particularly notable for pulmonary embolism (PE) (ROR 1.90, 95% CI 1.69-2.12) and deep vein thrombosis (DVT) (ROR 1.36, 95% CI 1.16-1.59). In this real-world study, tofacitinib use was associated with a higher reporting risk of VTE events compared with TNFi in RA patients. These findings underscore the need for careful patient selection and risk assessment when prescribing tofacitinib. Further prospective studies are warranted to confirm these associations and explore the underlying mechanisms.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275081","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}

引用次数: 0

Global hotspots and trends in AMPA receptor research (2000-2025): a bibliometric and visualization analysis. 全球AMPA受体研究热点与趋势（2000-2025）：文献计量与可视化分析。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-11 DOI: 10.1007/s00210-025-04679-7

Yunsheng Liu, Rongde Zhong, Xianlin Wu, Jinfang Zhang, Zengwei Kou

{"title":"Global hotspots and trends in AMPA receptor research (2000-2025): a bibliometric and visualization analysis.","authors":"Yunsheng Liu, Rongde Zhong, Xianlin Wu, Jinfang Zhang, Zengwei Kou","doi":"10.1007/s00210-025-04679-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04679-7","url":null,"abstract":"AMPA receptors (AMPARs) are critical excitatory ionotropic glutamate receptors involved in synaptic transmission, plasticity, and various neurological disorders. From 2000 to present (up to 2025), extensive research has explored their roles in brain function and disease, yet a comprehensive bibliometric analysis of this field is lacking. This study aims to provide a systematic bibliometric overview of AMPAR research from 2000 to present, identifying key trends, influential contributors, and emerging hotspots to guide future investigations. Data were retrieved from Web of Science, PubMed, and Scopus, encompassing 37,000 distinct publications. Bibliometric tools (CiteSpace, VOSviewer, and Bibliometrix) were employed to analyze publication trends, country/institution contributions, journal metrics, author productivity, and keyword clusters. The United States led in publication output (6,142 articles) and citations (410,626), followed by China and Japan. The Journal of Neuroscience and Neuron were the top journals, while Huganir RL was the most cited author. Research hotspots evolved from fundamental AMPAR properties (e.g., subunit composition) to disease associations (e.g., Alzheimer's, depression) and therapeutic strategies (e.g., AMPAR modulators). Keyword analysis revealed four themes: biochemical properties, physiological functions, pathological roles, and therapeutic targets. AMPAR research has transitioned from basic neurophysiology to translational applications, with growing emphasis on neurological and psychiatric disorders. Future directions include elucidating native AMPAR complexes, trafficking dynamics, and precision therapeutics. This study highlights the field's progression and underscores the need for interdisciplinary collaboration to address unresolved challenges.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275386","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}

引用次数: 0

Elevated PXDC1 expression linked to poor prognosis and abnormalities in PD-L1 regulation and NK cell function in colorectal cancer. PXDC1表达升高与结直肠癌预后不良、PD-L1调节和NK细胞功能异常有关。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-11 DOI: 10.1007/s00210-025-04628-4

Wei Cheng, Di Gao, Junyu Ren, Jiaxin Liu

{"title":"Elevated PXDC1 expression linked to poor prognosis and abnormalities in PD-L1 regulation and NK cell function in colorectal cancer.","authors":"Wei Cheng, Di Gao, Junyu Ren, Jiaxin Liu","doi":"10.1007/s00210-025-04628-4","DOIUrl":"https://doi.org/10.1007/s00210-025-04628-4","url":null,"abstract":"Colorectal cancer (CRC) remains a prevalent malignancy with suboptimal treatment outcomes, underscoring the need for novel prognostic and therapeutic biomarkers. This research is the initial exploration into the role of PXDC1 in CRC, analyzing its differential expression, prognostic significance, and correlation with tumor-infiltrating immune cells through transcriptomics, spatial transcriptomics, and single-cell genomics. Immunohistochemistry (IHC) staining confirmed that PXDC1 expression was notably higher in CRC tissues compared to normal tissues, highlighting its potential role in CRC progression. Functional assays, including CCK8, colony formation, scratch assays, and flow cytometry, showed that PXDC1 knockdown in CRC cells inhibited proliferation, migration, and induced apoptosis. Additional analyses utilizing bioinformatics, Western blotting, co-culture experiments, molecular docking, and immunofluorescence revealed a positive correlation between PXDC1 and PD-L1 expression. Knockdown of PXDC1 enhanced the tumor-killing capacity of NK-92 cells and promoted increased cytokine release. These results indicate that PXDC1 is pivotal in CRC progression, where its elevated levels are linked to poor prognosis, tumor growth, immune cell infiltration, and NK cell impairment. This highlights PXDC1's potential as a significant prognostic biomarker and an attractive therapeutic target for CRC, offering opportunities for more precise and targeted treatment approaches.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275313","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}

引用次数: 0

The publish or perish, publish and perish, publish then perish, and now retract and perish cultures in academia. 发表或灭亡，发表或灭亡，发表然后灭亡，现在学术界的文化撤回并灭亡。

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-10 DOI: 10.1007/s00210-025-04651-5

Jaime A Teixeira da Silva, Serhii Nazarovets

{"title":"The publish or perish, publish and perish, publish then perish, and now retract and perish cultures in academia.","authors":"Jaime A Teixeira da Silva, Serhii Nazarovets","doi":"10.1007/s00210-025-04651-5","DOIUrl":"https://doi.org/10.1007/s00210-025-04651-5","url":null,"abstract":"The publish-or-perish (POP) culture in academic publishing has become ingrained for several reasons and may be a phenomenon that is difficult to erase simply because publishing remains the most visible form of recognition for scientists, who use both publishing and the recognition it confers to remain relevant while securing their status, employment, funding, visibility, and other benefits. Although scientific publishing has immeasurable benefits when it represents thoroughly conducted research or an integrated philosophy, when observed through the prism of POP culture, a negative connotation is associated with it. As the POP adage implies, if one does not publish, then one may figuratively and intellectually perish (i.e., publish and perish), and when this transcends to a literal plane, the adage publish then perish is born. At a more extreme level, and no longer driven by the desire to publish, the retraction of intellect or literature due to error or misconduct has diversified POP culture by adding a layered adage of retract and perish, where the latter may occur both figuratively and literally. In this essay, an attempt is made to identify several factors that may induce POP culture and the impact it has on individual careers, knowledge creation, the benevolence of scientific endeavor, and the well-being of science, society, and Humanity.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274960","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}

引用次数: 0

The immunoregulatory role of lncRNA UCA1: a pan-cancer perspective with a focus on colorectal cancer. lncRNA UCA1的免疫调节作用：以结直肠癌为重点的泛癌症视角

IF 3.1 4区医学

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2025-10-10 DOI: 10.1007/s00210-025-04588-9

Fatemeh Maghool, Parisa Kadkhodaei Elyaderani, Ahmadreza Rajabi, Fatemeh Balangi, Aida Heidari, Samane Mohammadzadeh, Mohammad Hassan Emami, Pouria Samadi

{"title":"The immunoregulatory role of lncRNA UCA1: a pan-cancer perspective with a focus on colorectal cancer.","authors":"Fatemeh Maghool, Parisa Kadkhodaei Elyaderani, Ahmadreza Rajabi, Fatemeh Balangi, Aida Heidari, Samane Mohammadzadeh, Mohammad Hassan Emami, Pouria Samadi","doi":"10.1007/s00210-025-04588-9","DOIUrl":"https://doi.org/10.1007/s00210-025-04588-9","url":null,"abstract":"Long non-coding RNA UCA1 has emerged as a critical regulator in cancer biology. This study comprehensively investigates UCA1 expression and its functional relevance across multiple cancer types, with a focus on colorectal cancer (CRC). Pan-cancer analyses were conducted using data retrieved from TCGA, GTEx, cBioPortal, and BEST databases, integrated via R programming. Single-cell RNA sequencing data from CellxGene platform were used to explore cell-type-specific UCA1 expression. Functional enrichment, co-expression networks, genomic alterations, diagnostic profile, CpG methylation, immune associations, and drug response profiles as well as experimental validation were also assessed. UCA1 was significantly overexpressed in at least 10 tumor types, most notably in CRC. Single-cell analysis revealed UCA1 expression across epithelial, stromal, and immune cell populations, including T cells and plasma cells. UCA1 correlated with genes like GRHL3 and KLK8, implicating roles in tissue development, adhesion, and motility. Genomic analyses revealed copy number amplifications (e.g., 17q12) and altered methylation patterns. Elevated UCA1 expression was linked to poorer prognosis in several cancers and positively correlated with recurrence and progression risk in CRC and other tumors. Immune analysis showed UCA1's association with regulatory T cells, chemokines, and immune checkpoints, indicating an immunosuppressive role. Additionally, UCA1 impacted drug resistance and sensitivity across therapies. UCA1 plays a multifaceted role in cancer progression, immune modulation, and therapy response. Its expression in diverse cell types within the tumor microenvironment and association with clinical outcomes supports its potential as a prognostic biomarker and therapeutic target, especially in CRC.","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274992","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}

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