European journal of pharmacology最新文献_第2页

Tulipalin A suppressed the pro-inflammatory polarization of M1 macrophage and mitigated the acute lung injury in mice via interference DNA binding activity of NF-κB 郁金香苷 A 通过干扰 NF-κB 的 DNA 结合活性，抑制了 M1 巨噬细胞的促炎极化，减轻了小鼠的急性肺损伤。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-05 DOI: 10.1016/j.ejphar.2024.177034

{"title":"Tulipalin A suppressed the pro-inflammatory polarization of M1 macrophage and mitigated the acute lung injury in mice via interference DNA binding activity of NF-κB","authors":"","doi":"10.1016/j.ejphar.2024.177034","DOIUrl":"10.1016/j.ejphar.2024.177034","url":null,"abstract":"<div><div>Acute lung injury (ALI) is an inflammatory disorder accompanied by higher morbidity and mortality. The pathological mechanism of ALI has been reported to be associated with the release of inflammatory cytokines by macrophages. Sesquiterpene lactones (SLs) represent the principal anti-inflammatory components of many natural products. Tulipalin A is a natural small molecule and a conserved moiety in anti-inflammatory SLs. However, the anti-inflammatory potential of Tulipalin A has yet to be fully disclosed. The present study aims to investigate TulipalinA's anti-inflammatory activity and underlying mechanisms <em>in vitro</em> and <em>in vivo</em>. Tulipalin A suppressed inflammatory responses in lipopolysaccharide (LPS)-stimulated bone marrow-derived primary macrophages and ameliorated LPS-induced ALI in mice. Mechanistically, Tulipalin A directly targets the NF-<em>κ</em>B p65 and disrupts its DNA binding activity, thereby impeding the activation of NF-<em>κ</em>B. Inhibition of NF-<em>κ</em>B attenuated M1 polarization of macrophages, consequently suppressing the production of pro-inflammatory mediators and ameliorating the onset and progression of ALI. These findings suggest Tulipalin A's potential to mitigate inflammatory disorders like ALI via targeting NF-<em>κ</em>B p65 and disrupting its DNA binding activity.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pharmacological modulation of transglutaminase 2 in the unilateral ureteral obstruction mouse model 在单侧输尿管梗阻小鼠模型中对转谷氨酰胺酶 2 进行药理调节。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-05 DOI: 10.1016/j.ejphar.2024.177037

{"title":"Pharmacological modulation of transglutaminase 2 in the unilateral ureteral obstruction mouse model","authors":"","doi":"10.1016/j.ejphar.2024.177037","DOIUrl":"10.1016/j.ejphar.2024.177037","url":null,"abstract":"<div><h3>Background</h3><div>Transglutaminase 2 (TG2) is a multifunctional enzyme involved in fibrosis by promoting transforming-growth-factor-β1 and crosslinking of extracellular matrix proteins. These functions are dependent on the open conformation, while the closed state of TG2 can induce vasodilation. We explored the putative protective role of TG2 in its closed state on development of renal fibrosis and blood pressure (BP) regulation.</div></div><div><h3>Methods</h3><div>We studied the unilateral ureteral obstruction (UUO) mouse model treated with LDN27219, which promotes the closed conformation of TG2. Mice were subjected to 7 days UUO or sham operation and treated with vehicle (n = 10), LDN27219 (15 mg/kg/12 h, n = 9) or candesartan (5 mg/kg/day, n = 10) as a clinically comparator. Renal expression of TG2 and pro-fibrotic mediators were evaluated by Western blotting, qPCR and histology, and BP by tail-cuff measurements.</div></div><div><h3>Results</h3><div>Obstructed kidneys showed increased mRNA and protein expression of fibronectin, collagen 3α1 (Col3α1), α-smooth muscle actin and collagen staining. Despite increased renal TG2 mRNA, protein expression was reduced in all UUO groups, but with increased transamidase activity in the vehicle and candesartan groups. LDN27219 reduced mRNA expression of fibronectin and Col3α1, but their protein expression remained unchanged. In contrast to LDN27219, candesartan lowered BP without affecting expression of pro-fibrotic biomarkers.</div></div><div><h3>Conclusion</h3><div>Renal TG2 mRNA and protein expression levels seem dissociated, with transamidase activity being increased. LDN27219 influences kidney pro-fibrotic markers at the mRNA level and attenuates transamidase activity but without affecting collagen content or BP. Our findings suggest that TG2 in its closed conformation has anti-fibrotic effects at the molecular level.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of hippocampal miRNA expression by intestinal flora in anxiety-like mice 肠道菌群对焦虑样小鼠海马 miRNA 表达的调控

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-05 DOI: 10.1016/j.ejphar.2024.177016

{"title":"Regulation of hippocampal miRNA expression by intestinal flora in anxiety-like mice","authors":"","doi":"10.1016/j.ejphar.2024.177016","DOIUrl":"10.1016/j.ejphar.2024.177016","url":null,"abstract":"<div><div>This study investigated the possible interaction between gut flora and miRNAs and the effect of both on anxiety disorders. The model group was induced with chronic restraint stress (CRS) and each group was tested for anxiety-like behaviour by open field test and elevated plus maze test. Meanwhile, the gut flora was analysed by 16S rRNA high-throughput sequencing. The miRNAs in hippocampus were analysed by high-throughput sequencing, and the key miRNAs were obtained by using the method of bioinformatics analysis. PCR was used to verify the significantly related key miRNAs. Spearman correlation analysis was used to explore the correlation between behaviour, key miRNAs and differential gut microbiota. The 16S rRNA high-throughput sequencing result showed that the gut flora was dysregulated in the model group. In particular, Verrucomicrobia, <em>Akkermansia</em>, <em>Anaerostipes</em>, <em>Ralstonia</em>, <em>Burkholderia</em> and <em>Anaeroplasma</em> were correlated with behaviour. The results of miRNA high-throughput sequencing analysis and bioinformatics analysis showed that 7 key miRNAs influenced the pathogenesis of anxiety, and qRT-PCR results were consistent with the high-throughput sequencing results. Mmu-miR-543-3p and mmu-miR-26a-5p were positively correlated with Verrucomicrobia, <em>Akkermansia</em> and <em>Anaerostipes</em>. Therefore, we infer that chronic stress caused the decrease of <em>Akkermansia</em> abundance, which may aggravate the decrease of mmu-miR-543-3p and mmu-miR-26a-5p expression, leading to the increase of SLC1A2 expression. In conclusion, gut flora has played an important influence on anxiety with changes in miRNAs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unique cardiometabolic factors in women that contribute to modified cardiovascular disease risk 导致心血管疾病风险改变的女性独特的心脏代谢因素。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-05 DOI: 10.1016/j.ejphar.2024.177031

{"title":"Unique cardiometabolic factors in women that contribute to modified cardiovascular disease risk","authors":"","doi":"10.1016/j.ejphar.2024.177031","DOIUrl":"10.1016/j.ejphar.2024.177031","url":null,"abstract":"<div><div>Major risk factors of cardiovascular disease (CVD) include hypertension, obesity, diabetes mellitus and metabolic syndrome; all of which are considered inflammatory conditions. Women are disproportionately affected by inflammatory conditions, with sex differences emerging as early as adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy and menopause, are hypothesized to promote a pro-inflammatory state in women. Moreover, women who have experienced inflammatory-type conditions such as polycystic ovarian syndrome (PCOS), gestational diabetes or pre-eclampsia, have a cardiometabolic phenotype that pre-disposes to increased risk of myocardial infarction, stroke and coronary heart disease. Women with no notable CVD risk factors are often relatively protected from CVD pre-menopause; but overtake men in risk of major cardiovascular events when the cardiovascular protective effects of oestrogen begin to wane. Sex differences and female-specific factors have long been considered challenging to study and this has led to an underrepresentation of females in clinical trials and lack of female-specific data from pre-clinical studies. However, there is now a clear prerogative to include females at all stages of research, despite inherent complexities and potential variability in data. This review explores recent advancements in our understanding of CVD in women. We summarise the underlying factors unique to women that can promote CVD risk factors, ultimately contributing to CVD burden and the emerging therapies aimed to combat this.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glibenclamide reverses cardiac damage and NLRP3 inflammasome activation associated with a high refined sugar diet 格列本脲可逆转与高精制糖饮食相关的心脏损伤和NLRP3炎性体激活。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-04 DOI: 10.1016/j.ejphar.2024.177035

{"title":"Glibenclamide reverses cardiac damage and NLRP3 inflammasome activation associated with a high refined sugar diet","authors":"","doi":"10.1016/j.ejphar.2024.177035","DOIUrl":"10.1016/j.ejphar.2024.177035","url":null,"abstract":"<div><div>Increased energy intake from carbohydrates has been associated with major cardiovascular outcomes. Mice fed a highly-refined carbohydrate (HC) diet develop cardiac hypertrophy and inflammation. During cardiac injury, NLRP3 inflammasome is activated which results in a local inflammatory response. In this study, we hypothesized that a nom-hypoglycemic dose of glibenclamide may reverses sugar diet-induced cardiac damage by NRLP3 inflammasome inhibition. Mice were fed the HC diet for eight weeks and divided into a group treated with glibenclamide (20 mg/kg, gavage) and another with vehicle for four weeks. Afterward, hearts were excised for morphometric analysis and <em>ex vivo</em> function determination. NLRP3 inflammasome activation was investigated by western blotting and <em>in situ</em> fluorescent detection of reactive oxygen species (ROS) and active caspase-1. The HC diet promotes heart hypertrophy and collagen deposition, which were reverted by glibenclamide without ameliorating HC diet-induced insulin resistance. Changes in cardiac performance were observed <em>in vivo</em> by invasive catheterization and in Langendorff-perfused hearts due to the HC diet, which were prevented by glibenclamide. Hearts from HC diet mice had increased levels of NLRP3 and cleaved IL-1β. Glibenclamide reversed ROS production and caspase-1 activity induced by HC diet. These findings suggest glibenclamide's cardioprotective effects on heart damage caused by the HC diet are related to its inhibitory action on the NLRP3 inflammasome.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Protein kinase C (PKC) inhibitor Calphostin C activates PKC in a light-dependent manner at high concentrations via the production of singlet oxygen 蛋白激酶 C（PKC）抑制剂钙泊三嗪 C 在高浓度下通过产生单线态氧以光依赖的方式激活 PKC。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-04 DOI: 10.1016/j.ejphar.2024.177036

{"title":"Protein kinase C (PKC) inhibitor Calphostin C activates PKC in a light-dependent manner at high concentrations via the production of singlet oxygen","authors":"","doi":"10.1016/j.ejphar.2024.177036","DOIUrl":"10.1016/j.ejphar.2024.177036","url":null,"abstract":"<div><div>Calphostin C (Cal-C) is a protein kinase C (PKC) inhibitor that binds to its C1 domain. The aim of the present study was to elucidate the action of Cal-C in addition to PKC inhibition. First, we confirmed that Cal-C at low concentrations (<200 nM) inhibit phorbol ester-induced PKC translocation and G-protein-coupled receptor (GPCR)-mediated PKC activation. Cal-C at higher concentrations (>2 μM) increased intracellular calcium ion concentrations ([Ca<sup>2+</sup>]<sub>i</sub>) in a concentration-dependent manner. The origin of this increase is the mobilization of the endoplasmic reticulum (ER), which does not involve GPCR or ryanodine receptors. Cal-C at high concentrations also cause structural changes in the ER, such as the formation of vacuoles and aggregates, and calcium leakage from the ER. At 2 μM, Cal-C translocated a calcium-sensitive PKCα. Studies using a C-kinase activity reporter and a myristoylated alanine-rich protein kinase C substrate fused with green fluorescent protein (GFP) have also revealed that Cal-C at high concentrations activate PKC in living cells. Additionally, the PKC-activating effects of Cal-C were light-dependent. Finally, studies using Si-DMA, an indicator of singlet oxygen, showed that Cal-C at high concentrations generated singlet oxygen, causing structural changes in the ER and leakage of calcium into the cytosol, which triggered PKC activation. This study confirms the novel action of Cal-C, solely considered a PKC inhibitor. Cal-C acted as a PKC inhibitor at low concentrations and a PKC activator at high concentrations by generating singlet oxygen in a light-dependent manner, suggesting that Cal-C can be used in photodynamic therapy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Phloridzin prevents diabetic cardiomyopathy by reducing inflammation and oxidative stress 氯氮平通过减轻炎症和氧化应激预防糖尿病心肌病

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-04 DOI: 10.1016/j.ejphar.2024.177032

{"title":"Phloridzin prevents diabetic cardiomyopathy by reducing inflammation and oxidative stress","authors":"","doi":"10.1016/j.ejphar.2024.177032","DOIUrl":"10.1016/j.ejphar.2024.177032","url":null,"abstract":"<div><div>Oxidative stress and inflammation significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Persistent inflammatory stimuli drive the progression of myocardial fibrosis and impaired cardiac function. Phloridzin (Phl), a natural compound, demonstrates both anti-inflammatory and antioxidant properties. Nevertheless, its therapeutic potential and underlying mechanisms in DCM remain unclear. This study aimed to elucidate the mechanisms through which Phl inhibited myocardial fibrosis and exerted its antioxidative effects. The impact of Phl on DCM was evaluated using a high-fat/high-sugar diet combined with streptozotocin to induce an animal model and an in vitro H9C2 cell model stimulated by high glucose (HG). Untargeted metabolomics identified potential mechanisms underlying myocardial fibrosis. Phl treatment significantly enhanced left ventricular ejection fraction (EF%) and shortening fraction (FS%), while reducing myocardial injury markers, such as lactate dehydrogenase and creatine phosphokinase-MB, and suppressing myocardial collagen fiber accumulation. Simultaneously, Phl attenuated myocardial inflammation via inhibition of MyD88/NF-κB signaling, modulated the Nrf2/GPX4 axis to counter oxidative stress, and mitigated ferroptosis. In vitro, Phl inhibited high glucose-induced myocardial hypertrophy and fibrosis in H9C2 cells, while also repressing NF-κB activation in cardiomyocytes. Metabolomic profiling revealed that Phl ameliorated DCM through modulation of glycerophospholipid metabolic pathways, linking these metabolic shifts to enhanced antioxidant capacity, thereby reflecting its ability to reduce oxidative stress in the myocardium. Collectively, Phl provides cardioprotective effects by alleviating inflammation and oxidative damage.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Scoparone alleviates nonalcoholic fatty liver disease by modulating the PPARα signaling pathway Scoparone 可通过调节 PPARα 信号通路缓解非酒精性脂肪肝。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-04 DOI: 10.1016/j.ejphar.2024.177033

{"title":"Scoparone alleviates nonalcoholic fatty liver disease by modulating the PPARα signaling pathway","authors":"","doi":"10.1016/j.ejphar.2024.177033","DOIUrl":"10.1016/j.ejphar.2024.177033","url":null,"abstract":"<div><div>Scoparone (Scop), a natural compound derived from <em>Artemisia capillaris</em> Thunb, has demonstrated efficacy in improving nonalcoholic fatty liver disease (NAFLD). This study aims to explore the underlying mechanism. NAFLD was induced by a high-fat diet in C57BL/6J mice, followed by an 8-week treatment with Scop. The effect of Scop on mice NAFLD was assessed. mRNA sequencing of liver tissues was performed to identify potential targets, which were validated through <em>in vitro</em> experiments using palmitic acid-induced AML12 hepatocytes. The results demonstrated that Scop promoted lipid metabolism, insulin sensitivity, and liver function, and alleviated inflammation in NAFLD mice. mRNA sequencing identified the peroxisome proliferator-activated receptor α (PPARα) signaling pathway as a target of Scop, which was further confirmed by <em>in vivo</em> and <em>in vitro</em> experiments. Molecular docking studies showed that Scop could bind stably to human PPARα. In summary, Scop was proven to alleviate lipid metabolism dysfunction and inflammation by targeting the PPARα signaling pathway, which provides a basis for its potential application in NAFLD treatment.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Retraction notice to “A novel compound DSC suppresses lipopolysaccharide-induced inflammatory responses by inhibition of Akt/NF-κB signalling in macrophages" [Eur. J. Pharmacol. 708/1–3 (2013) 8–13] 新型化合物 DSC 通过抑制巨噬细胞中的 Akt/NF-κB 信号抑制脂多糖诱导的炎症反应》的撤稿通知[《欧洲药理学杂志》708/1-3 (2013) 8-13]。

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-04 DOI: 10.1016/j.ejphar.2024.176993

引用次数: 0

Small-molecule mediated MuRF1 inhibition protects from doxorubicin-induced cardiac atrophy and contractile dysfunction 小分子介导的 MuRF1 抑制可防止多柔比星诱发的心肌萎缩和收缩功能障碍

IF 4.2 3区医学

European journal of pharmacology Pub Date : 2024-10-02 DOI: 10.1016/j.ejphar.2024.177027

{"title":"Small-molecule mediated MuRF1 inhibition protects from doxorubicin-induced cardiac atrophy and contractile dysfunction","authors":"","doi":"10.1016/j.ejphar.2024.177027","DOIUrl":"10.1016/j.ejphar.2024.177027","url":null,"abstract":"<div><div>Cancer chemotherapy induces cell stress in rapidly dividing cancer cells to trigger their growth arrest and apoptosis. However, adverse effects related to cardiotoxicity underpinned by a limited regenerative potential of the heart limits clinical application: In particular, chemotherapy with doxorubicin (DOXO) causes acute heart injury that can transition to persisting cardiomyopathy (DOXO-CM). Here, we tested if MuRF1 inhibition (“MuRFi”) was able to attenuate DOXO-CM. To mimic DOXO chemotherapy, we treated mice over four weeks with five DOXO injections, resulting in a cumulative dosage of 25 mg/kg. At day 28, mice had lower body and heart weights, reduced cardiac cross-sectional myofibrillar areas (CSAs), and disturbed functional ejection fractions (EFs) and fractional shortenings (FS) as indicated by echocardiography (ECHO). In contrast, mice with a 1 g/kg Myomed#205 spiked diet, a previously described experimental MuRFi therapy, showed lower DOXO-CM at day 28, and also reduced acute DOXO cardiac injury at day 7 (single DOXO dose; 15 mg/kg). Underlying molecular signatures using Western blot (WB) assays showed at day 28 reduced phospho-AKT (AKTp) and phospo-4EBP1 (4 EBP1p) levels following DOXO that were normalized following MuRFi treatment. Taken together, our data suggest that MuRFi treatment is suitable to attenuate DOXO-CM by preserving AKTp and 4 EBP1p levels in DOXO stressed cardiomyocytes, thereby supporting de novo protein translation and cardiomyocyte survival under translational arrest stress.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0