Acta Pharmaceutica最新文献

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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 : 2024-12-17 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":"https://doi.org/10.2478/acph-2025-0002","url":null,"abstract":"<p><p>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), <i>p =</i> 0.001; LDL-C/WMD = 0.449, 95%CI: (0.200, 0.698), <i>p</i> < 0.001]. In addition, this study also observed that statins may reduce UAE levels [WMD = -46.814, 95% CI: (-71.767, -21.861), <i>p</i> < 0.001]. Finally, the survey indicated that statins may be associated with an ESRD reduction [HR = 0.884, 95% CI: (0.784, 0.998), <i>p</i> = 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.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-17","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 : 2024-12-17 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":"https://doi.org/10.2478/acph-2025-0003","url":null,"abstract":"<p><p>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 <i>Escherichia coli</i> 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 <i>E. coli</i> 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.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-17","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
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 : 2024-12-17 DOI: 10.2478/acph-2025-0001
Lu-Qin Guo, Lan Zhou, Sheng-Nan Li, Juan Bai, Ling-Li Shi, Fang Hua, Peng Zhou
{"title":"Integrating network pharmacology and <i>in vivo</i> model to reveal the cardiovascular protective effects of kaempferol-3-<i>O</i>-rutinoside on heart failure.","authors":"Lu-Qin Guo, Lan Zhou, Sheng-Nan Li, Juan Bai, Ling-Li Shi, Fang Hua, Peng Zhou","doi":"10.2478/acph-2025-0001","DOIUrl":"https://doi.org/10.2478/acph-2025-0001","url":null,"abstract":"<p><p>Kaempferol-3-<i>O</i>-rutinoside (KR) has an excellent cardioprotective effect, but its mechanism of action is not clear. Network pharmacology was used to predict the signaling pathways, whereas molecular docking was used for preliminary validation of KR binding to targets. AMI model rats with ligated left anterior descending coronary arteries were established. HE staining was used to detect pathological changes, and ELISA was used to detect the expression of TNF-α and IL-6. Network pharmacology results showed PI3K-AKT signaling pathway may be the main mechanism, and molecular docking predicted that KR could bind strongly to the PI3K and AKT. KR could significantly reduce cardiac pathological changes, decrease the level of TNF-α and IL-6, and enhance the mRNA and protein expressions of PI3K and AKT. KR ameliorates HF after AMI by enhancing the expressions of PI3K and AKT, which will be helpful in elucidating the mechanism of KR through multiple techniques.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833399","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
Tannic acid elicits differential gene regulation in prostate cancer apoptosis. 单宁酸在前列腺癌凋亡过程中引发不同的基因调控。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0020
Sinan Kandir, Sevtap Karakurt, Çiğdem Gökçek-Saraç, Serdar Karakurt
{"title":"Tannic acid elicits differential gene regulation in prostate cancer apoptosis.","authors":"Sinan Kandir, Sevtap Karakurt, Çiğdem Gökçek-Saraç, Serdar Karakurt","doi":"10.2478/acph-2024-0020","DOIUrl":"https://doi.org/10.2478/acph-2024-0020","url":null,"abstract":"<p><p>Prostate cancer is a significant global health concern that requires innovative therapeutic investigations. Here, the potential anticancer properties of tannic acid were evaluated by examining its effects on apoptosis in prostate cancer cell lines. PC-3 and LnCaP prostate adeno carcinoma cells, along with PNT1A prostate control cells, were cultured and divided into untreated and tannic acid-treated groups. Cell proliferation, cytotoxicity, and effects of tannic acid on the cell death mechanism were evaluated. mRNA expression levels of 84 genes were explored in cells following tannic acid treatment. Notably, tannic acid-induced down-regulation of several pro-survival genes, including <i>ATM, BCL2, BCL2A1, BIK, BIRC2, BIRC3, BRE, CASP3, CASP6, CASP8, CHEK2, CRADD, PPIA, RPA3, TNFSF18, TRAF1, TRAF2, TRAF4,</i> and <i>TRAF5</i> in both cell lines. Moreover, tannic acid treatment led to the up-regulation of various pro-apoptotic genes, such as <i>BCL10, BIRC3, BNIP3, CASP1, CASP5, CD40, CIDEB, DAPK2, FASLG, GADD45A, MYD88, RPA 3, TNFRSF10D, TNFRSF17, TNFRSF8, TNFSF13B, TNFSF4, TNFSF7, TNFSF8, TNFSF9, TP53, TRAF1, and TRAF2</i> in both PC-3 and LnCap cells. These findings highlight tannic acid's ability to induce apoptosis in prostate cancer cells through pro-apoptotic pathways. This study concludes that tannic acid selectively inhibits prostate cancer cell growth.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"539-550"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278658","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 tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver. 酪氨酸激酶抑制剂来伐替尼被大鼠细胞色素P450氧化,并影响它们在大鼠肝脏中的表达。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0027
Radek Indra, Sandra Jelínková, Katarína Kollárová, Petra Zahumenská, Josef Dvořák, Šárka Dušková, Helena Dračínská
{"title":"The tyrosine kinase inhibitor lenvatinib is oxidized by rat cytochromes P450 and affects their expression in rat liver.","authors":"Radek Indra, Sandra Jelínková, Katarína Kollárová, Petra Zahumenská, Josef Dvořák, Šárka Dušková, Helena Dračínská","doi":"10.2478/acph-2024-0027","DOIUrl":"https://doi.org/10.2478/acph-2024-0027","url":null,"abstract":"<p><p>Lenvatinib is an orally effective tyrosine kinase inhibitor used to treat several types of tumors, including progressive, radioiodine-refractory differentiated thyroid cancer and advanced renal cell carcinoma. Although this drug is increasingly used in therapy, its metabolism and effects on the organism are still not described in detail. Using the rat as an experimental animal model, this study aimed to investigate the metabolism of lenvatinib by rat microsomal enzymes and cytochrome P450 (CYPs) enzymes recombinantly expressed in Supersomes<sup>TM</sup> <i>in vitro</i> and to assess the effect of lenvatinib on rat CYP expression <i>in vivo</i>. Two metabolites, <i>O</i>-desmethyl lenvatinib, and lenvatinib <i>N</i>-oxide, were produced by rat CYPs <i>in vitro</i>. CYP2A1 and 2C12 were found to be the most effective in forming <i>O</i>-desmethyl lenvatinib, while CYP3A2 was found to primarily form lenvatinib <i>N</i>-oxide. The administration of lenvatinib to rats caused changes in the expression of mRNA and protein, as well as the activity of various CYPs, particularly in an increase in CYP1A1. Thus, the administration of lenvatinib to rats has an impact on the level of CYPs.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"441-459"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278659","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
PPIA, HRPT1, and PGK1 genes as the appropriate combination for RT-qPCR normalization in alveolar and femoral bone remodeling in olanzapine-treated rats. 将 PPIA、HRPT1 和 PGK1 基因作为奥氮平治疗大鼠牙槽骨和股骨头重塑中 RT-qPCR 正常化的适当组合。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0029
Saranda Disha-Ibrahimi, Gorazd Drevenšek, Martina Drevenšek, Janja Marc, Irena Prodan Žitnik
{"title":"PPIA, HRPT1, and PGK1 genes as the appropriate combination for RT-qPCR normalization in alveolar and femoral bone remodeling in olanzapine-treated rats.","authors":"Saranda Disha-Ibrahimi, Gorazd Drevenšek, Martina Drevenšek, Janja Marc, Irena Prodan Žitnik","doi":"10.2478/acph-2024-0029","DOIUrl":"https://doi.org/10.2478/acph-2024-0029","url":null,"abstract":"<p><p>Reliable gene expression analysis in bone remodeling studies requires an appropriate selection of internal controls, <i>i.e.</i> stable reference genes for the normalization of quantitative real-time PCR (RT-qPCR), the most common method used for quantifying gene expression measurements. Even the most widely used reference genes can have variable expression under different experimental conditions, or in different tissue types or treatment regimes, so selecting appropriate controls is a key step in ensuring reliable results. The aim of this research was to identify the most stable reference gene(s) for the study of olanzapine modulated bone remodeling in rats. RNA was isolated from the maxillary alveolar and femoral bones of olanzapine or placebo-treated Wistar rats and transcribed to cDNA. The expression of 12 candidate reference genes was assessed by RT-qPCR. Their expressions were analysed using GeNorm, NormFinder, BestKeeper and delta Ct algorithms, and by the comprehensive ranking method. <i>PPIA, HRPT1</i> and <i>PGK1</i> were the most stably expres sed reference genes and the combination of the three genes was optimal for normalization. This study is the first to identify the optimal reference genes for research in olanzapine-exposed rats, which serve as a pivotal benchmark for enhancing the accuracy and reliability of future RT-qPCR expression in bone studies.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"511-524"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278656","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
Synthesis and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s). 作为青霉素结合蛋白抑制剂的新型 3-氨基-4-取代单环 ß-内酰胺的合成与生化评估。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0024
Katarina Grabrijan, Nika Strašek Benedik, Alen Krajnc, Krištof Bozovičar, Damijan Knez, Matic Proj, Irena Zdovc, Izidor Sosič, Carlos Contreras-Martel, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec
{"title":"Synthesis and biochemical evaluation of new 3-amido-4-substituted monocyclic ß-lactams as inhibitors of penicillin-binding protein(s).","authors":"Katarina Grabrijan, Nika Strašek Benedik, Alen Krajnc, Krištof Bozovičar, Damijan Knez, Matic Proj, Irena Zdovc, Izidor Sosič, Carlos Contreras-Martel, Andréa Dessen, Martina Hrast Rambaher, Stanislav Gobec","doi":"10.2478/acph-2024-0024","DOIUrl":"https://doi.org/10.2478/acph-2024-0024","url":null,"abstract":"<p><p>In the final phases of bacterial cell wall synthesis, penicillin-binding proteins (PBPs) catalyze the cross-linking of peptidoglycan. For many decades, effective and non-toxic β-lactam antibiotics have been successfully used as mimetics of the d-Ala-d-Ala moiety of the natural substrate and employed as irreversible inhibitors of PBPs. In the years following their discovery, the emergence of resistant bacteria led to a decline in their clinical efficacy. Using Staudinger cycloaddition, we synthesized a focused library of novel monocyclic β-lactams in which different substituents were introduced at the C4 position of the β-lactam ring, at the C3 amino position, and at the N1 lactam nitrogen. In biochemical assays, the compounds were evaluated for their inhibitory effect on the model enzyme PBP1b from <i>Streptococcus pneumoniae</i>. Upon investigation of the antibacterial activity of the newly prepared compounds against ESKAPE pathogens, some compounds showed moderate inhibition. We also examined their reactivity and selectivity in a biochemical assay with other enzymes that have a catalytic serine in the active site, such as human cholinesterases, where they also showed no inhibitory activity, highlighting their specificity for bacterial targets. These compounds form the basis for further work on new monocyclic β-lactams with improved antibacterial activity.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"423-440"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278657","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
Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs. 三叶青通过抑制 JNK/c-Jun/MMPs 减轻皮肤光老化损伤。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0025
Xuan Fei, Lele Zixin Yang, Jingjing Zhang, Xiang Li, Mengtian Pan, Guangchen Xu, Cuixia Zhang, Fei Liu, Weirong Fang
{"title":"Trifarotene alleviates skin photoaging injury by inhibition of JNK/c-Jun/MMPs.","authors":"Xuan Fei, Lele Zixin Yang, Jingjing Zhang, Xiang Li, Mengtian Pan, Guangchen Xu, Cuixia Zhang, Fei Liu, Weirong Fang","doi":"10.2478/acph-2024-0025","DOIUrl":"https://doi.org/10.2478/acph-2024-0025","url":null,"abstract":"<p><p>Long-term exposure to ultraviolet (UV) radiation induces skin photoaging, which manifests as oxidative stress, inflammation, and collagen degradation. Multiple approaches (topical or systemic retinoids, antioxidants, alpha-hydroxy acids, laser, surgery) are used in the treatment of photoaged skin, and the use of topical retinoids is currently a primary clinical treatment. Previous studies revealed that retinoic acid promotes keratinocyte proliferation and reduces melanin deposition and matrix metalloproteinase (MMP) secretion; it also causes potential allergic and inflammatory damage to the skin. This study aimed to investigate the therapeutic effects and mechanisms of trifarotene, a functional retinoic acid analog, on UV-irradiated photoaging ICR and BALB/c nude mice and UVB photodamaged human epidermal keratinocyte (HaCaT) cells by examining indicators such as collagen, oxidoreductase, and inflammatory factor presence through histochemical staining, Western blot, and ELISA. Results suggested that trifarotene significantly reduced UV-induced photoaging in mouse skin tissue, potentially by reducing oxidative stress damage and inflammatory factor release, and inhibiting melanin deposition and collagen degradation by downregulating MMP expression. Concentrations of malondialdehyde, tyrosinase, interleukin-6, interleukin- 12, and tumor necrosis factor-alpha in photoaged skin decreased, while SOD content in photodamaged HaCaT cells significantly increased. Trifarotene (3.3 μmol L-1) inhibited phosphorylated JNK and c-Jun expression both independently and collaboratively with the JNK activator anisomycin, demonstrating that trifarotene mitigates UV-induced collagen degradation and apoptosis through inhibition of the JNK/c-Jun/MMPs signaling pathway.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"461-478"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278660","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
Alternative buffer systems in biopharmaceutical formulations and their effect on protein stability. 生物制药配方中的替代缓冲体系及其对蛋白质稳定性的影响。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0022
Blaž Lebar, Mitja Zidar, Janez Mravljak, Roman Šink, Aleš Žula, Stane Pajk
{"title":"Alternative buffer systems in biopharmaceutical formulations and their effect on protein stability.","authors":"Blaž Lebar, Mitja Zidar, Janez Mravljak, Roman Šink, Aleš Žula, Stane Pajk","doi":"10.2478/acph-2024-0022","DOIUrl":"https://doi.org/10.2478/acph-2024-0022","url":null,"abstract":"<p><p>The formulation of biopharmaceutical drugs is designed to eliminate chemical instabilities, increase conformational and colloidal stability of proteins, and optimize interfacial stability. Among the various excipients involved, buffer composition plays a pivotal role. However, conventional buffers like histidine and phosphate buffers may not always be the optimal choice for all monoclonal antibodies (mAbs). In this study, we investigated the effects of several alternative buffer systems on seven different mAbs, exploring various combinations of ionic strengths, concentrations of the main buffer component, mAb concentrations, and stress conditions. Protein stability was assessed by analyzing soluble aggregate formation through size exclusion chromatography. At low protein concentrations, protein instability after temperature stress was exclusively observed in the bis-TRIS/ glucuronate buffer. Conversely, freeze-thaw stress led to a significant increase in aggregate formation in tested formulations, highlighting the efficacy of several alternative buffers, particularly arginine/ citrate, in preserving protein stability. Under temperature stress, the introduction of arginine to histidine buffer systems provided additional stabilization, while the addition of lysine resulted in protein destabilization. Similarly, the incorporation of arginine into histi-dine/HCl buffer further enhanced protein stability during freeze--thaw cycles. At high protein concentrations, the histidine/citrate buffer emerged as one of the most optimal choices for addressing temperature and light-induced stress. The efficacy of histidine buffers in combating light stress might be attributed to the light-absorbing properties of histidine molecules. Our findings demonstrate that the development of biopharmaceutical formulations should not be confined to conventional buffer systems, as numerous alternative options exhibit comparable or even superior performance.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"479-493"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278650","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
Personalization of thiopurine therapy: Current recommendations and future perspectives. 硫嘌呤疗法的个性化:当前建议和未来展望。
IF 2.1 4区 医学
Acta Pharmaceutica Pub Date : 2024-09-14 Print Date: 2024-09-01 DOI: 10.2478/acph-2024-0030
Dunja Urbančič, Flaka Pasha, Alenka Šmid, Irena Mlinarič-Raščan
{"title":"Personalization of thiopurine therapy: Current recommendations and future perspectives.","authors":"Dunja Urbančič, Flaka Pasha, Alenka Šmid, Irena Mlinarič-Raščan","doi":"10.2478/acph-2024-0030","DOIUrl":"https://doi.org/10.2478/acph-2024-0030","url":null,"abstract":"<p><p>Despite great therapeutic advances in the field of biologics, small synthetic molecules such as thiopurines, including azathioprine, mercaptopurine, and thioguanine, remain an important therapeutic pillar in the treatment of inflammatory bowel disease, other autoimmune disorders, and cancer. This review presents the latest guidelines for thiopurine administration, highlighting the importance of individualized therapy guided by pharmacogenomics. It emphasizes dose adjustment based on nudix hydrolase 15 (<i>NUDT15</i>) and thiopurine <i>S</i>-methyltransferase (<i>TPMT</i>) genotype, along side thiopurine <i>S</i>-methyltransferase activity and thiopurine metabolic profile. In addition, the article takes a critical look at emerging research in the field of thiopurine pharmaco genomics featuring novel genetic markers and technological developments in genetic testing. Finally, the potential of integrated approaches that combine genetic, meta bolic, and clinical factors to further individualize thiopurine therapy is highlighted.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"74 3","pages":"355-381"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278655","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
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