Current molecular pharmacology最新文献

{"title":"Network Pharmacology and Bioinformatics of Flavonoids from <i>Scutellaria baicalensis stems</i>: Mitigating Aβ-Induced Cognitive Impairment in Rats <i>via</i> the MEK-ERK-CREB Pathway.","authors":"Yan Chen, Shuai Ma, Jing Huo, Shengkai Ding, Qianqian Liu, Chen Li, Yinhui Yao, Yazhen Shang","doi":"10.2174/0118761429381010250512060455","DOIUrl":"https://doi.org/10.2174/0118761429381010250512060455","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the effects and mechanisms of <i>Scutellaria baicalensis flavonoids</i> (SSF) on passive avoidance learning and memory deficits induced by composite amyloid-β proteins (Aβ) via the MEK-ERK-CREB signaling pathway in rats based on network pharmacology and bioinformatics.</p><p><strong>Methods: </strong>Network pharmacology and bioinformatics identified target pathways. An Alzheimer's disease model was induced in male wistar rats using Aβ_25-35, AlCl₃, and RHTGF-β₁(referred to as compound Aβ). Memory impairment was confirmed with the Morris water maze. Modeled rats were assigned to a control group and three SSF-treated groups for 33 days. Passive avoidance learning abilities were assessed with a step-down test, and p-crebser133 expression in the hippocampus was detected via immunohistochemistry. Real-time qPCR and western blotting measured mRNA and protein levels of c-Raf, MEKs, Rsk, and zif268 in the hippocampus and cortex.</p><p><strong>Results: </strong>Pathways such as the calcium signaling pathway, Apelin signaling pathway and cAMP signaling pathway were highlighted by KEGG analysis. The model had an 83.30% success rate. Model rats showed dry coats and unresponsiveness, while SSF treatment improved appearance and behavior. In passive avoidance tests, model rats made more errors and had shorter latencies (P < 0.01). They also showed decreased p-CREBSer133 and increased c-Raf, Rsk, and P-MEKs levels (P < 0.01), with reduced Zif268 (P < 0.01). SSF reversed these effects, enhancing p-CREBSer133 and Zif268 while regulating c-Raf, Rsk, and P-MEKs (P < 0.01).</p><p><strong>Conclusion: </strong>SSF ameliorates learning and memory impairments induced by composite Aβ, acting through the MEK-ERK-CREB pathway in rats.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulation of Soluble Guanylyl Cyclase (sGC) by Cinaciguat Attenuates Sepsis- Induced Cardiac Injury.","authors":"Wanqian Li, Cheng Zheng, Xijiang Zhang, Binhui Wang, Enjian Shen, Lingjun Wang, Guang Chen, Ronghai Lin","doi":"10.2174/0118761429387280250506114040","DOIUrl":"https://doi.org/10.2174/0118761429387280250506114040","url":null,"abstract":"<p><strong>Background: </strong>Cinaciguat is a soluble Guanylyl Cyclase (sGC) activator that plays a crucial role in cardiovascular diseases. Previous research has shown that cinaciguat is involved in the progression of cardiomyopathy, which encompasses cardiac enlargement, heart dysfunction, and doxorubicin-induced heart damage. However, its therapeutic potential in sepsis-induced cardiomyopathy remains unknown.</p><p><strong>Objectives: </strong>This study examined the impact of cinaciguat on Lipopolysaccharide (LPS)-induced myocardial injury and the underlying molecular mechanisms.</p><p><strong>Methods: </strong>The mice model was established through intraperitoneal injection of LPS (10 mg/kg), and an <i>in vitro</i> model was generated by stimulating H9C2 cells with LPS (10 μg/ml) for 12 h. Subsequently, the sGC activator cinaciguat was used to assess its effects on LPS-induced cardiac injury. Additionally, echocardiography was conducted 12 hours after modeling to analyze cardiac function in mice. We used various methods to evaluate inflammation, and apoptosis, including Enzyme-Linked Immunosorbent Assay (ELISA), terminal deoxynucleotidyl transferase-mediated deoxyuridine Triphosphate Nick End Labeling (TUNEL) assay, Hematoxylin and Eosin (H&E) staining, western blotting and Real-Time Polymerase Chain Reaction (RT-PCR). Additionally, the protein kinase cGMP-dependent 1 (PRKG1)/cAMP-Response Element Binding protein (CREB) signaling pathway and Mitochondrial Ferritin (FtMt) in LPS-induced cardiac injury was assessed via Western blot analysis.</p><p><strong>Results: </strong>LPS-induced cardiac dysfunction and increased levels of cardiac injury markers Cardiac Troponin T (cTnT) <i>in vivo</i> . This change was accompanied by an increase in inflammatory cytokines through Interleu-1β (IL-1β), Tumor Necrosis Factor α (TNF-α), and Interleu-6 (IL-6). The expression of apoptosis, such as cleaved caspase-3, Bax, and Bcl-2, was also upregulated. However, these effects were reversed via treatment with cinaciguat. Additionally, cinaciguat alleviated LPS-induced cardiac inflammation and apoptosis by activating the PRKG1/CREB signaling pathway, and promoting FtMt expression. The same results were also obtained in H9C2 cardiomyocytes.</p><p><strong>Conclusion: </strong>We demonstrated that cinaciguat alleviated LPS-induced cardiac dysfunction, inflammation, and apoptosis through the PRKG1/CREB/FtMt pathway, thereby protecting against LPS-induced cardiac injury. This study identified a new strategy for treating cardiac injury caused by sepsis.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ergothioneine Suppresses Amyloid Β-Induced Tau Phosphorylation and Cytotoxicity by Inactivating Glycogen Synthase Kinase-3β in Cultured Neurons.","authors":"Fumiya Shibagaki, Yusei Hayashi, Satoshi Matsumoto, Noritaka Nakamichi","doi":"10.2174/0118761429387340250507055903","DOIUrl":"https://doi.org/10.2174/0118761429387340250507055903","url":null,"abstract":"<p><strong>Background: </strong>Amyloid-beta (Aβ) oligomers, formed by Aβ aggregation, are the causative agent of Alzheimer's disease and induce the hyperphosphorylation of tau protein (Tau) and neurotoxicity. The antioxidant ergothioneine (ERGO) is transferred to the brain after oral ingestion and protects against Aβ- induced neurotoxicity and cognitive dysfunction. However, the impact of ERGO on Aβ oligomer-induced Tau phosphorylation remains unclear.</p><p><strong>Objective: </strong>To investigate the effects of ERGO on Aβ-induced Tau phosphorylation and their mechanism in neurons.</p><p><strong>Method: </strong>SH-SY5Y cells differentiated into cholinergic neuron-like cells or primary cultured neurons derived from the murine hippocampus were pretreated with ERGO and exposed to Aβ_25-35 oligomers. Cytotoxicity was evaluated by assessing the chemiluminescence of dead cell-derived proteases. The expression of phosphorylated (p-) Tau at serine 396, p-glycogen synthase kinase-3 beta (GSK-3β) at serine 9, amyloid precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme 1 (BACE1; β-secretase), and nicastrin, which is a component protein of the γ-secretase complex, was assessed by western blotting.</p><p><strong>Result: </strong>Differentiated SH-SY5Y cells exhibited increased neurite outgrowth and mRNA expression of <i>choline acetyltransferase</i>, and showed cholinergic neuron-like characteristics compared with those of undifferentiated cells. ERGO significantly suppressed the Aβ_25-35 oligomer-induced increased cytotoxicity and p-Tau expression in differentiated SH-SY5Y cells and cultured hippocampal neurons. ERGO recovered the decreased expression of p-GSK-3β at serine 9, indicating its inactivation, and the increased expression of APP, BACE1, and nicastrin induced by Aβ_25-35 oligomer exposure in cultured hippocampal neurons. These ERGO effects on Aβ_25-35 oligomers were inhibited by treatment with LY294002, which activated GSK-3β.</p><p><strong>Conclusion: </strong>ERGO may suppress the increased expression of p-Tau and proteins involved in Aβ production induced by Aβ oligomers by inactivating GSK-3β, thereby mitigating neurotoxicity.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tangeretin in the Treatment of Pulmonary Fibrosis: Current Advances and Future Perspectives.","authors":"Ling-Jie Wang, Peng-Fei Guo, Yi-Zhao Chen, Hong-Wang Yan, Xue-Lin Zhang","doi":"10.2174/0118761429385520250508041438","DOIUrl":"https://doi.org/10.2174/0118761429385520250508041438","url":null,"abstract":"<p><p>Pulmonary fibrosis seriously endangers human health, with its incidence and mortality rates steadily increasing. Current treatment methods have limitations. This review focused on the research progress and future prospects of tangeretin in the treatment of pulmonary fibrosis. Tangeretin, a compound derived from the peel of citrus fruits, has garnered attention in pulmonary fibrosis research due to its unique chemical structure and its background in traditional medical applications. This paper discussed the pathological mechanisms of pulmonary fibrosis, including the initiation and persistent inflammation, abnormal activation and proliferation of fibroblasts, imbalance in extracellular matrix [ECM] metabolism, and the cycle of oxidative stress injury. Tangeretin has shown potential therapeutic effects, including anti-inflammation, regulation of ECM metabolism, and antioxidative stress activities. This paper reviewed the current research progress and possible therapeutic effects of tangeretin on pulmonary fibrosis and proposed future research directions for its application.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Mechanisms of STAT3 in GBM and its Impact on TMZ Resistance.","authors":"Guangyao Lv, Xueying Li, Hongtu Deng, Jianqiao Zhang, Xinfu Gao","doi":"10.2174/0118761429386400250415053351","DOIUrl":"https://doi.org/10.2174/0118761429386400250415053351","url":null,"abstract":"<p><p>STAT3, a key member of the Signal Transducer and Activator of Transcription (STAT) family, plays a vital role in the development and progression of glioblastoma (GBM), as well as in the resistance to the chemotherapy drug temozolomide (TMZ). This review outlines the dysregulation of STAT3 in GBM, focusing on its activation mechanisms and its contribution to TMZ resistance. STAT3 can be activated by cytokines, like IL-6, growth factors, and membrane receptors, like EGFR. In GBM, constitutively active STAT3 enhances tumor growth and therapy resistance. Specifically, resistance to TMZ, a standard chemotherapeutic agent for GBM, is facilitated by STAT3-induced expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase and anti-apoptotic proteins like Bcl-2, as well as through the regulation of microRNAs. To combat TMZ resistance in GBM, strategies that inhibit STAT3 activity have been explored. Recent advancements, such as the use of small molecule inhibitors targeting STAT3 and its upstream or downstream regulators, RNA-based therapies, as well as the development of nanocarriers for targeted delivery of STAT3-<i>targeting small interfering RNA</i> across the blood-brain barrier, have demonstrated significant potential in enhancing the sensitivity of GBM to TMZ. These targeted therapies hold promise for improving the treatment outcomes of patients with GBM.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIPK1/RIPK3/MLKL Necrosome Contributes to the Sepsis-Induced Cardiorenal Necroptotic Inflammatory Injury and Mortality.","authors":"Bahar Tunctan, Muhammed Ahmed-Reda Elosman, Sefika Pinar Senol, Elif Ikiz, Tuba Kara","doi":"10.2174/0118761429374574250415114715","DOIUrl":"https://doi.org/10.2174/0118761429374574250415114715","url":null,"abstract":"<p><strong>Introduction: </strong>Due to its critical role in inflammation and necroptotic cell death, RIPK1 has been considered a prominent therapeutic drug target for managing a wide variety of diseases, including sepsis. Therefore, we aimed to investigate whether the RIPK1-driven necroptotic pathway contributes to the nitrosative stress-mediated cardiorenal inflammatory necroptotic injury and mortality using RIPK1 inhibitor, Nec-1s, in the murine sepsis model induced by LPS.</p><p><strong>Methods: </strong>Experiments were performed using mice injected intraperitoneally with DMSO or Nec-1s with saline and/or LPS. Following euthanasia and 6 hours after the injection of these agents, arteriovenous blood samples, hearts, and kidneys of the animals were collected. Serum MPO, iNOS, CKMB, creatinine, and HMGB1 levels were measured by ELISA. Associated proteins were measured by immunoblotting. H&E staining was used to evaluate histopathological changes in the tissues. In the mortality studies, the mice were monitored every 6 hours for mortality up to 96 hours after saline, LPS, DMSO, and/or Nec-1s injection.</p><p><strong>Results: </strong>In the LPS-injected mice, a rise in serum MPO, iNOS, CK-MB, creatinine, and HMGB1 levels was associated with the enhanced expression/activity of RIPK1/RIPK3/MLKL necrosome, HMGB1, iNOS, nitrotyrosine, gp91^phox, and p47^phox, in addition to scores related to histopathological changes in their tissues. Nec-1s attenuated the LPS-induced changes. Mortality rates of 10%, 50%, and 60% were observed at the 24^th, 36^th, and 48^th hours, respectively, in the LPS-treated mice. When endotoxemic mice were treated with Nec-1s, mortality rates were 60%, 90%, and 100% at 18, 30, and 42 hours, respectively.</p><p><strong>Conclusion: </strong>These findings suggest that RIPK1/RIPK3/MLKL necrosome contributes to not only LPS-induced nitrosative stress-mediated cardiorenal inflammatory necroptotic injury, but also mortality.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Isorhamnetin: Targeting MAPK and NF-κB Pathways to Mitigate LPS-Induced Inflammation.","authors":"Abdelrahim Alqudah, Muna Barakat, Lujain F Alzaghari, Esam Qnais, Omar Gammoh, Mohammad Alqudah, Alaa Aa Aljabali, Sireen Abdul Rahim Shilbayeh","doi":"10.2174/0118761429385248250409060550","DOIUrl":"https://doi.org/10.2174/0118761429385248250409060550","url":null,"abstract":"<p><p>Introduction Chronic inflammation may result in mucosal damage, presenting as pain, edema, convulsions, and fever symptoms. This study investigated the anti-inflammatory characteristics of isorhamnetin (ISO) and its potential as a medicinal agent. Method In this study, in vitro tests were performed in which macrophages were activated with lipopolysaccharide (LPS) to evaluate the effect of ISO on inflammation. We concentrated on quantifying the synthesis of pro-inflammatory cytokines, interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF-α], as well as mediators, such as nitric oxide [NO] and prostaglandin E2 [PGE2], in LPS-stimulated RAW 264.7 cells. Results The findings indicated that ISO significantly decreased levels of NO and PGE2 while maintaining cellular integrity. ISO reduced the synthesis of pro-inflammatory cytokines in a dose-dependent manner. Moreover, ISO treatment decreased mRNA levels of inducible nitric oxide synthase [iNOS] and cyclooxygenase-2 [COX-2], which were enhanced following LPS exposure. Mechanistic investigations revealed that the antiinflammatory properties of ISO were facilitated by the inhibition of phosphorylation in the mitogen-activated protein kinase [MAPK] family and the downregulation of nuclear factor-kappa B inhibitor [IκB-α] within both the MAPK and nuclear factor-kappa B [NF-κB] pathways. Conclusion These findings establish ISO as a viable alternative for treating inflammatory diseases by specifically inhibiting essential inflammatory pathways.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cilia Plays a Pivotal Role in the Hypersecretion of Airway Mucus in Mice.","authors":"Yulin Liu, Tingting Liu, Ling Ruan, Danli Zhu, Yijing He, Jing Jia, Yirong Chen","doi":"10.2174/0118761429368288250401054301","DOIUrl":"https://doi.org/10.2174/0118761429368288250401054301","url":null,"abstract":"<p><strong>Background: </strong>Airway mucus hypersecretion is a prominent pathophysiological characteristic observed in chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma. It is a significant risk factor for lung dysfunction and impaired quality of life. Therefore, it is crucial to investigate changes in the major genes expressed in the lungs during airway mucus hypersecretion. Such investigations can help to identify genetic targets for the development of effective treatments to manage airway mucus hypersecretion and improve clinical outcomes for those affected by these respiratory disorders.</p><p><strong>Objective: </strong>Our study aims to identify changes in the expression of key genes in the lungs during airway mucus hypersecretion in mice.</p><p><strong>Methods: </strong>Thirty male C57BL/6 mice were randomly allocated into two groups. The Pyocyanin (PCN) group was intranasally infected with 25 μl of pyocyanin solution (1 μg/μl), while the phosphate-buffered saline (PBS) group received 25 μl of PBS intranasally once daily. The lung tissue of mice was extracted after 21 days for the purpose of identifying causal genes through a combination of transcriptomic and proteomic analysis. Finally, we validated the differentially expressed proteins using qRT-PCR and western blot.</p><p><strong>Results: </strong>Our findings revealed significant alterations in 35,268 genes and 7,004 proteins within the lung tissue of mice treated with PCN. Pathway enrichment analysis, utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, showed that the differentially expressed proteins were mainly associated with apoptosis, galactose metabolism, and asthma, among the overlapping genes and proteins. To validate the results of the transcriptomic and proteomic analyses, we used qRT-PCR to examine the expression levels of fourteen differentially expressed proteins (DEPs), namely Fpr1, Ear1, Lama3, Col19a1, Spag16, Ropn1l, Dnali1, Cfap70, Ear2, Drc1, Ifit3, Lrrc23, Slpi, and Fam166b. Subsequently, we confirmed the expression of Spag16, Dnali1, and Ropn1l by western blotting.</p><p><strong>Conclusions: </strong>Our study identified three DEPs, namely Spag16, Dnali1, and Ropn1l, which are closely associated with the movement and organization of cilia. This study provides novel insights for the development of therapeutic interventions targeting airway mucus hypersecretion.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloe-Emodin Relieves Myocardial Intracellular Calcium Homeostasis Imbalance Induced by High-Fat Diet <i>via</i> Protein Arginine Methyltransferase/ Ca²⁺/Calmodulin- Dependent Protein Kinase II Signaling Pathway in Rats.","authors":"Wen Li, Juan Hu, Ye Yuan, Zhimin Du, Jia Wang, Yilian Yang, Bing Shao, Jiapan Wang, Mingxiu Zhang, Chunlei Duan, Zhen Chen, Wenjie Liao, Xueqi He","doi":"10.2174/0118761429364907250319054353","DOIUrl":"https://doi.org/10.2174/0118761429364907250319054353","url":null,"abstract":"<p><p>Background Chronic high-fat diets (HFDs) lead to an imbalance of calcium homeostasis in cardiomyocytes, which contributes to the development of myocardial ischemia-reperfusion injury, dilated cardiomyopathy, and other cardiovascular diseases. Aloe-emodin (AE) is an anthraquinone component isolated from aloe, rhubarb, and cassia seed, having cardiovascular protective, hepatoprotective, anti-inflammatory, and other pharmacological effects. Objective This study aimed to explore the specific role of AE in obesity/hyperlipidemia-induced myocardial intracellular calcium homeostasis imbalance. Methods Wistar rats (male, 220 ± 20 g) were fed HFD for four weeks and AE (100 mg/kg) was administrated for six weeks after confirmation of the HFD model. Serum lipids, reactive oxygen species levels, malondialdehyde levels, and superoxide dismutase levels were measured by commercial biochemical kits. Electrocardiograms of rats were recorded with the BL-420F biological function experimental system. Calcium transients and resting intracellular Ca²⁺ concentrations were determined by the Langendorff-perfused heart model. Protein levels of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), protein arginine methyltransferase 1 (PRMT1), and cardiac Ca²⁺ handling proteins were evaluated by western blot analysis. Results HFD-induced hearts exhibited a reduced amplitude of Ca2+ transients and increased resting levels of [Ca2+] in the heart; AE treatment significantly improved these parameters. Furthermore, the HFD-induced heart showed downregulation of PRMT1, upregulation of CaMKII, and abnormalities in the levels of Ca²⁺ handling proteins. All these deleterious changes were significantly suppressed by the AE treatment. Moreover, AE treatment prevented palmitic acid (PA)-induced calcium overload in H9C2 cells; this effect was reduced by the application of an inhibitor of PRMT1. Conclusion Taken together, this study demonstrates that AE could alleviate HFD/PA-induced myocardial intracellular calcium homeostasis imbalance via the PRMT1/CaMKII signaling pathway.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of miRNAs in Podocyte Injury in Diabetic Nephropathy: Mechanisms and Clinical Applications.","authors":"Shan Hu, Jiafu Yan, Qiong Yuan, Tianjiao Meng, Zhi Cai, Yuanshuai Huang, Yuhan Wang","doi":"10.2174/0118761429363169250313083148","DOIUrl":"https://doi.org/10.2174/0118761429363169250313083148","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is one of the most frequent complications of diabetes and, if left uncontrolled, can progress to renal failure. In the early stage of DKD, significant pathological changes occur in podocytes, leading to proteinuria. However, the mechanism of pathological changes in podocytes has not been clarified. Existing clinical diagnostic methods tend to overlook these subtle pathophysiological changes in the early stages, leading to missed optimal treatment time. Moreover, existing treatment methods are limited. Emerging evidence strongly suggests that podocyte injury is associated with distinct specific miRNA expression profiles that precede the onset of overt proteinuria and glomerular filtration rate decline. This review explores the role of microRNAs in podocyte damage-related pathways in DKD, such as reactive oxygen species (ROS) production and inflammatory responses. Furthermore, we discuss the potential clinical application of miRNAs as molecular markers and their feasibility as a molecular therapy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}