Acta Pharmaceutica最新文献

Design, synthesis, and evaluation of a novel fluorescent probe for competitive fluorescence polarization assay to screen galectin-8 inhibitors. 一种新型荧光探针的设计、合成和评价，用于竞争性荧光偏振法筛选半乳糖凝集素-8抑制剂。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-30 DOI: 10.2478/acph-2025-0010

Edvin Purić, Marina Marinović, Zala Kojek, Barbro Kahl-Knutson, Hakon Leffler, Ulf J Nilsson, Marko Anderluh, Janez Mravljak

引用次数: 0

Optimization of 6-(trifluoromethyl)pyrimidine derivatives as TLR8 antagonists. 6-（三氟甲基）嘧啶衍生物TLR8拮抗剂的优化。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-30 DOI: 10.2478/acph-2025-0011

Nika Strašek Benedik, Valerij Talagayev, Troy Matziol, Ana Dolšak, Izidor Sosič, Günther Weindl, Gerhard Wolber, Matej Sova

{"title":"Optimization of 6-(trifluoromethyl)pyrimidine derivatives as TLR8 antagonists.","authors":"Nika Strašek Benedik, Valerij Talagayev, Troy Matziol, Ana Dolšak, Izidor Sosič, Günther Weindl, Gerhard Wolber, Matej Sova","doi":"10.2478/acph-2025-0011","DOIUrl":"https://doi.org/10.2478/acph-2025-0011","url":null,"abstract":"Toll-like receptors (TLRs) are essential for the innate immune system as they recognize pathogen-associated molecular patterns and trigger immune responses. Overactivation of TLR8 by endogenous nucleic acids is associated with the development of autoimmune diseases and promotes inflammatory responses. This study presents the design, synthesis, and evaluation of a series of TLR8 antagonists based on the optimization of previously reported 6-(trifluoromethyl)pyrimidin-2-amines, with targeted modifications to further explore structure-activity relationships (SAR) and increase potency. A two-step synthesis involving nucleophilic aromatic substitution and Suzuki coupling was used to prepare two series of new compounds. The biological evaluation revealed that compounds 14 and 26 exhibited promising TLR8 antagonistic activity with IC 50 values of 6.5 and 8.7 μmol L-1, respectively. Compound 14 showed reduced cell viability at higher concentrations, while compound 26 showed no cytotoxic effects, making it a promising candidate for further investigation.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959648","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

FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer. METTL3在YTHDF1的辅助下调控FOXD2-AS1影响食管癌的增殖和凋亡。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0009

Zijin Wang, Xing Chen Liu, Zhen Gya Gao, Wo Da Shi, Wen Cai Wang

{"title":"FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer.","authors":"Zijin Wang, Xing Chen Liu, Zhen Gya Gao, Wo Da Shi, Wen Cai Wang","doi":"10.2478/acph-2025-0009","DOIUrl":"https://doi.org/10.2478/acph-2025-0009","url":null,"abstract":"This study aims to investigate the regulatory mechanisms of METTL3, YTHDF1, and the long non-coding RNA FOXD2-AS1 in the proliferation and apoptosis of esophageal cancer, with the goal of providing a basis for molecular diagnosis and targeted therapies. Gene expression was evaluated using qRT-PCR (METTL3/14) and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and Transwell assay were employed to assess cell proliferation and apoptosis. The EpiQuik m6A RNA Methylation Quantification Kit was utilized to quantify total m6A levels. The interaction between YTHDF1, FOXD2-AS1, and METTL3 was confirmed using RNA Binding Protein Immunoprecipitation (RIP), Co-Immunoprecipitation (CO-IP), and RNA pull-down assays. Methylated RNA Immuno preci pitation (MeRIP) was employed to assess the m6A modification levels of FOXD2-AS1. Tissue samples from animal models were analyzed via Hematoxylin-eosin staining (HE) staining and immunohisto-chemistry to assess METTL3 expression. The expression of METTL3 was up-regulated in esophageal cancer tissues and cells. Flow cytometry and CCK-8 detection showed that silencing METTL3 could inhibit the proliferation of esophageal cancer cells but accelerate their apoptosis. MeRIP-qPCR and Prediction of m6A-modified sites indicated that METTL3 regulated the m6A modification of FOXD2-AS1. In vitro and in vivo experiments showed that YTHDF1 binds to METTL3 and regulates the m6A modification of FOXD2-AS1 to affect esophageal cancer. Our results indicate that METTL3 regulates FOXD2-AS1 in an m6A-dependent manner through its interaction with YTHDF1, thereby influencing EC proliferation and apoptosis. This suggests a potential therapeutic target for the treatment of esophageal cancer.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"69-86"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957214","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 impact of blood lipids and statins on renal function and mortality in patients with diabetic nephropathy: A meta-analysis. 血脂和他汀类药物对糖尿病肾病患者肾功能和死亡率的影响：荟萃分析。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0002

Dongqin Tian, Qian Chen, Lingli Zeng, Yan Hao

{"title":"The impact of blood lipids and statins on renal function and mortality in patients with diabetic nephropathy: A meta-analysis.","authors":"Dongqin Tian, Qian Chen, Lingli Zeng, Yan Hao","doi":"10.2478/acph-2025-0002","DOIUrl":"10.2478/acph-2025-0002","url":null,"abstract":"The aim of this study is to explore the impact of blood lipids and statins on renal function and all-cause mortality in patients with diabetic nephropathy (DN). PubMed, Embase, Web of Science, and Cochrane Library were systematically searched until April 9, 2024, for relevant studies of blood lipids and statins on renal function and all-cause mortality in patients with DN. After the selection, total cholesterol levels (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), serum creati-nine (SCR), end-stage renal disease (ESRD), and all-cause mortality indexes were extracted for finally meta-analysis. In total, 25 papers containing 21,411 patients with DN were finally included in this study. Levels of TC and LDL-C, which are continuous variables, were higher in DN patients who developed ESRD [TC/weighted mean difference (WMD) = 0.517, 95 % confidence interval (CI): (0.223, 0.812), p = 0.001; LDL-C/WMD = 0.449, 95%CI: (0.200, 0.698), p < 0.001]. In addition, this study also observed that statins may reduce UAE levels [WMD = -46.814, 95% CI: (-71.767, -21.861), p < 0.001]. Finally, the survey indicated that statins may be associated with an ESRD reduction [HR = 0.884, 95% CI: (0.784, 0.998), p = 0.045]. Blood lipids, particularly TC and LDL-C, may slow the progression of DN to ESRD. Besides, statins may protect the kidneys by lowering the excretion of UAE levels and reducing the risk of ESRD. Based on the above outcomes, the findings of this study provided robust evidence-based medical support for the future prevention, surveillance, and management of DN.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-22"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833403","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

Cloning, expression, and purification of recombinant AKR1D1 for therapeutic applications. 用于治疗的重组AKR1D1的克隆、表达和纯化。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0003

Kristina Shutevska, Aleksandra Kapedanovska Nestorovska

{"title":"Cloning, expression, and purification of recombinant AKR1D1 for therapeutic applications.","authors":"Kristina Shutevska, Aleksandra Kapedanovska Nestorovska","doi":"10.2478/acph-2025-0003","DOIUrl":"10.2478/acph-2025-0003","url":null,"abstract":"AKR1D1, a key enzyme in the aldo-keto reductase superfamily, plays a dual role in both steroid metabolism and bile acid synthesis by catalyzing the NADPH-dependent reduction of carbon-carbon double bonds, specifically converting 3-ketosteroid hormones into 5β-steroids. Positioned at the critical intersection of steroid hormone and bile acid metabolism, AKR1D1 has the potential to profoundly influence metabolic homeostasis and drug metabolism. Despite its importance, the enzyme's therapeutic implications and role in drug metabolism remain underexplored. This study presents an optimized methodology for the cloning, expression, and purification of AKR1D1 using an Escherichia coli expression system. We identified optimal conditions for ligation and precise DNA sequencing, emphasizing the need for lower DNA concentrations and higher purity. Protein expression was evaluated in E. coli strains BL21 and Rosetta, with the highest yields achieved under extended incubation at 25 °C with controlled IPTG concentrations. Using freshly transformed cells was essential for maintaining consistent protein expression. The enzyme's activity was confirmed using a spectrofluorometric assay, demonstrating efficient reduction of testosterone to 5β-DHT. This optimized methodology facilitates the production of AKR1D1 with high specific activity, establishing a valuable platform for future research. It enables a deeper investigation into AKR1D1's contributions to drug metabolism and its therapeutic potential.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"147-157"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833396","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

Comparative efficacy and safety of vedolizumab and antitumor necrosis factor alfa in patients with inflammatory bowel diseases: A meta‑analysis. vedolizumab和抗肿瘤坏死因子在炎症性肠病患者中的比较疗效和安全性：一项荟萃分析

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0004

Yafang Li, Jin Ding, Chong Lu, Yiping Hong, Qunying Wang

{"title":"Comparative efficacy and safety of vedolizumab and antitumor necrosis factor alfa in patients with inflammatory bowel diseases: A meta‑analysis.","authors":"Yafang Li, Jin Ding, Chong Lu, Yiping Hong, Qunying Wang","doi":"10.2478/acph-2025-0004","DOIUrl":"10.2478/acph-2025-0004","url":null,"abstract":"This meta-analysis directly compares the efficacy and safety of vedolizumab and tumor necrosis factor-α (TNF-α) inhibitors for patients with inflammatory bowel disease (IBD), contrary to the previous one which provided an indirect comparison. In this meta-analysis, only the studies that directly compared two treatments (vedolizumab and TNF-α inhibitors) to each other (head-to-head approach) were considered. A comprehensive literature search was conducted using the following databases: PubMed, Embase, the Cochrane Library, and Web of Science. The pooled estimates of efficacies and safety were calculated as relative risk (RR) and 95 % confidence interval (CI). The presence of bias in the published material was evaluated using Begg's test. Sensitivity analysis was used to evaluate the pooled results' robustness. In total, 32 eligible studies were finally included. Results showed that the efficacy of vedolizumab was superior to TNF-α inhibitors in clinical remission [1.26, 95 % CI: 1.15-1.39]. Moreover, the vedolizumab group showed a reduced incidence of severe adverse events (RR = 0.63, 95 % CI: 0.42-0.94) compared to TNF-α inhibitors. Our results revealed superior efficacy and safety of vedolizumab compared to TNF-α inhibitors, which provided direct evidence for the use of vedolizumab in IBD treatment. Future studies are needed to confirm our findings.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"23-40"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603302","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

Acute toxicity and hepatoprotective effect of Arum maculatum on rat liver cirrhosis induced with thioacetamide. 黄魔芋对硫乙酰胺致大鼠肝硬化的急性毒性及肝保护作用。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0007

Riyadh Zainadin Mawlood, Kamaran Abdoulrahman

引用次数: 0

Application of network pharmacology, bioinformatics, computational molecular docking, and experimental validation to study the anticancer effects of oleanolic acid in oral squamous carcinoma cells. 应用网络药理学、生物信息学、计算分子对接、实验验证等方法研究齐墩果酸对口腔鳞癌细胞的抗癌作用。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0005

Ting Yin, Hao Wang, Yaqin Zou

{"title":"Application of network pharmacology, bioinformatics, computational molecular docking, and experimental validation to study the anticancer effects of oleanolic acid in oral squamous carcinoma cells.","authors":"Ting Yin, Hao Wang, Yaqin Zou","doi":"10.2478/acph-2025-0005","DOIUrl":"https://doi.org/10.2478/acph-2025-0005","url":null,"abstract":"Oleanolic acid (OA) has demonstrated anticancer effects across various cancers, with some derivatives advancing to clinical trials. Howe ver, its precise mechanisms of action remain unclear, especially in oral squamous cell carcinoma (OSCC). This study employed network pharmacology, bioinformatics, molecular docking, dynamics simulations, and experimental validation to explore OA's anticancer effects in OSCC and elucidate its mechanism of action. OA's pharmacokinetic and physicochemical properties were assessed using SwissADME and Molsoft, revealing high oral bioavailability and GI absorption. SwissTargetPrediction and SuperPred identified protein targets, whereas GeneCards provided OSCC-related targets. A Venn diagram showed 34 overlapping targets between OA and OSCC. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network with 32 nodes and 164 edges, identifying HSP90AA1, STAT3, HSP90AB1, PI3KR1, and NFKB1 as key hub genes. Gene ontology and KEGG enrichment analyses highlighted relevant biological processes, molecular functions, and pathways. Molecular docking and dynamics simulations confirmed the strong binding of OA to hub targets. Experimental validation showed that OA inhibited cell viability and colony formation in a dose-dependent manner, induced apoptosis, and downregulated HSP90AA1, STAT3, and PI3KR1 proteins. In conclusion, this comprehensive study combining network pharmacology, bioinformatics, molecular simulations, and experimental assays provides valuable insights into OA's anticancer potential and detailed mechanism of action in OSCC.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"41-68"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952184","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

Untargeted metabolic analysis using LC-Q-TOF-MS and toxicity assessment of Eryngium foetidum in zebrafish embryos. LC-Q-TOF-MS法分析斑马鱼胚胎中胎氧的非靶向代谢及毒性评价。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0008

Romario Vázquez-Cancino, Sergio Rodríguez-Morales, Nelly Del Carmen Jiménez-Pérez, Omar Aristeo Peña-Morán, Litzia Cerón-Romero, Irma Sánchez-Lombardo, Alam Yair-Hidalgo, Nancy Romero Ceronio, Cuauhtémoc Alvarado-Sánchez, Oswaldo Hernández-Abreu

{"title":"Untargeted metabolic analysis using LC-Q-TOF-MS and toxicity assessment of Eryngium foetidum in zebrafish embryos.","authors":"Romario Vázquez-Cancino, Sergio Rodríguez-Morales, Nelly Del Carmen Jiménez-Pérez, Omar Aristeo Peña-Morán, Litzia Cerón-Romero, Irma Sánchez-Lombardo, Alam Yair-Hidalgo, Nancy Romero Ceronio, Cuauhtémoc Alvarado-Sánchez, Oswaldo Hernández-Abreu","doi":"10.2478/acph-2025-0008","DOIUrl":"https://doi.org/10.2478/acph-2025-0008","url":null,"abstract":"Toxicological studies of edible plant species are important to determine the safety of their consumption. Eryngium foetidum is an edible plant used in some countries for seasoning food and as a natural remedy in folk medicine. Despite this species' gastronomic and medicinal properties, the chemical composition and toxicity have been unclear. The objective of our investigation was to determine the toxic potential of E. foetidum in the zebrafish embryo model and identify the potential compounds involved in its toxicity by electrospray ionization liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry. Acute exposure of zebrafish embryos to n-hexane extract produced higher toxicity than the other extracts in a time- and concentration-dependent fashion (coagulated embryo). A 96-h median lethal concentration (LC 50) of 2.63 µg mL-1 (CI 95 % 0.58-28.5) was calculated by probit analysis. Caudal fin hypertrophy, head, yolk sac edema, caudal region, or somite malformations were observed. Secondary metabolites such as terpenes, polyphenols, and fatty acids were identified in the n-hexane extract. Also, pollutants such as diglycidyl resorcinol ether, diisopropyl adipate, and lauryl sulfate were found in the n-hexane extract. Our study revealed that chemical pollutants could be associated with the embryonic toxicity of the n-hexane extract of E. foetidum.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"133-146"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958002","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

Integrating network pharmacology and in vivo model to reveal the cardiovascular protective effects of kaempferol-3-O-rutinoside on heart failure. 整合网络药理学和体内模型，揭示山奈酚-3-O-芸香糖苷对心衰的心血管保护作用

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0001

Lu-Qin Guo, Lan Zhou, Sheng-Nan Li, Juan Bai, Ling-Li Shi, Fang Hua, Peng Zhou

引用次数: 0