Current Molecular Pharmacology - Volume 17, Issue 1, 2024
Volume 17, Issue 1, 2024
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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 and Ronghai LinBackground 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. Objectives T Read More
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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 and Yuhan WangDiabetic 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 ea Read More
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(R)-STU104 and Brefeldin-A Synergistically Enhance the Therapeutic Effect On IBD By Inhibiting the TAK1-MKK3-P38 Signaling Pathway
Authors: Haidong Li, Xiaoyan Shen, Xiaogang Qin and Yongxia LiuIntroduction Inflammatory Bowel Disease (IBD) imposes a huge burden on both patients and the society. Standard treatments are often ineffective and can lead to adverse effects. Biological Tumor Necrosis Factor (TNF-α) inhibitors, though effective, have issues with immunogenicity and high costs. Our study investigates the potential of Brefeldin A (BFA) and (R)-STU104 in treating IBD by targeting the Transforming Growth Fact Read More
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Network Pharmacology and Bioinformatics of Flavonoids from Scutellaria baicalensis stems: Mitigating Aβ-Induced Cognitive Impairment in Rats via the MEK-ERK-CREB Pathway
Authors: Yan Chen, Shuai Ma, Jing Huo, Shengkai Ding, Qianqian Liu, Chen Li, Yinhui Yao and Yazhen ShangIntroduction This study investigates the effects and mechanisms of Scutellaria baicalensis flavonoids (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. Methods Network pharmacology and bioinformatics identified target pathways. An Alzheimer's disease model was in Read More
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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 and Noritaka NakamichiBackground 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 pho Read More
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Regulatory Mechanisms of STAT3 in GBM and its Impact on TMZ Resistance
Authors: Guangyao Lv, Xueying Li, Hongtu Deng, Jianqiao Zhang and Xinfu GaoSTAT3, 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, growt Read More
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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 and Xue-Lin ZhangPulmonary 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 struct Read More
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Mechanistic Insights into Isorhamnetin: Targeting MAPK and NF-κB Pathways to Mitigate LPS-induced Inflammation
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 c Read More
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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 and Tuba KaraIntroduction 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 Read More
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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 and Yirong ChenBackground 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 iden Read More
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Upregulation of LncRNA WT1-AS Inhibits Tumor Growth and Promotes Autophagy in Gastric Cancer via Suppression of PI3K/Akt/mTOR Pathway
Authors: Xiaobei Zhang, Meng Jin, Xiaoying Yao, Jilan Liu, Yonghong Yang, Jian Huang, Guiyuan Jin, Shiqi Liu and Baogui ZhangBackgroundIncreasing evidence has highlighted the involvement of the imbalance of long non-coding RNAs in the development of gastric cancer (GC), which is one of the most common malignancies in the world. This study aimed to determine the role of lncRNA WT1-AS in the progression of GC and explore its underlying mechanism.MethodsThe expression of lncRNA WT1-AS in gastric cancer tissues was detected using RT-qP Read More
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Protective Effect of Platycodin D on Allergic Rhinitis in Mice through DPP4/JAK2/STAT3 Pathway Inhibition
Authors: Qiaojing Jia, Zhichang Liu, Caixia Wang, Bingyi Yang, Xiangjian Zhang, Chunguang Shan and Jianxing WangBackground: Allergic Rhinitis (AR) is an inflammatory condition characterized by nasal mucosa remodeling, driven by Immunoglobulin E (IgE). Platycodin D (PLD) exhibits a wide range of bioactive properties. Aim: The aim of this work was to investigate the potential protective effects of PLD on AR, as well as the underlying mechanisms. Methods: The anti-allergic and anti-inflammatory potential of PLD was investigated in an o Read More
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Aloe-Emodin Relieves Myocardial Intracellular Calcium Homeostasis Imbalance Induced by High-fat Diet via 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 and Xueqi HeBackground 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 ot Read More
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Doxazosin Attenuates Development of Testosterone Propionate-induced Prostate Growth by regulating TGF-β/Smad Signaling Pathway, Prostate-specific Antigen Expression and Reversing Epithelial-Mesenchymal Transition in Mice and Stroma Cells
Authors: YiDan Li, BingHua Tu, ZiTong Wang, ZiChen Shao, ChenHao Fu, JianQiang Hua, ZiWen Zhang, Peng Zhang, Hui Sun, ChenYan Mao and Chi-Ming LiuBackground Finasteride and doxazosin are used for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Epithelial–mesenchymal transition (EMT) and TGF-β/Smad signaling pathway play an important role in BPH, little is known about the growth inhibition and anti-fibrosis effects of doxazosin on the regulation of EMT and morphology in the prostate. Objectives The present study e Read More
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Empagliflozin Mitigates High Glucose-disrupted Mitochondrial Respiratory Function in H9c2 Cardiomyoblasts: A Comparative Study with NHE-1 and ROCK Inhibition
Authors: Cheng-I Cheng, Ming-Huei Chou, I-Ling Shih, Po-Han Chen and Ying-Hsien KaoBackground Hyperglycemia in patients with diabetes mellitus (DM) increases the risk of developing cardiomyopathy and heart failure. Elevation of sodium/proton exchanger-1 (NHE-1) expression and activity in cardiomyocytes leads to greater sensitivity to neurohormonal stimulation and cardiomyopathy, whereas inhibition of sodium-glucose cotransporter 2 (SGLT2) clinically benefits DM population in reducing heart failure Read More
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Neuroprotective Potential of Tanshinone-IIA in Mitigating Propionic Acid-induced Experimental Autism-like Behavioral and Neurochemical Alterations: Insights into c-JNK and p38MAPK Pathways
Authors: Kajal Sherawat, Sidharth Mehan, Zuber Khan, Aarti Tiwari, Ghanshyam Das Gupta and Acharan S. NarulaIntroductionAutism is a neurodevelopmental disorder associated with mitochondrial dysfunction, apoptosis, and neuroinflammation. These factors can lead to the overactivation of c-JNK and p38MAPK.MethodsIn rats, stereotactic intracerebroventricular (ICV) injection of propionic acid (PPA) results in autistic-like characteristics such as poor social interaction, repetitive behaviours, and restricted communication. Research has Read More
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Sirt1 Regulates Phenotypic Transformation of Diabetic Cardiac Fibroblasts through Akt/Α-SMA Pathway
Authors: Xiaomei Li, Shimeng Huang, Yuanbo Gao, Ying Wang, Siyu Zhao, Bing Lu and Aibin TaoAims: Cardiac fibrosis causes most pathological alterations of cardiomyopathy in diabetes and heart failure patients. The activation and transformation of cardiac fibroblasts (CFs) are the main pathological mechanisms of cardiac fibrosis. It has been established that Sirtuin1 (Sirt1) plays a protective role in the pathogenesis of cardiovascular disorders. This study aimed to ascertain the Sirt1 effect on the phenotypic t Read More
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Exploring the Immune-related Molecular Mechanisms Underlying the Comorbidity of Temporal Lobe Epilepsy and Major Depressive Disorder through Integrated Data Set Analysis
Authors: Shi Yan, Zhibin Han, Tianyu Wang, Aowen Wang, Feng Liu, Shengkun Yu, Lin Xu, Hong Shen, Li Liu, Zhiguo Lin and Meng NaBackground Temporal lobe epilepsy (TLE) and major depressive disorder (MDD) are prevalent and complex neurological disorders that affect individuals globally. Clinical and epidemiological studies indicate a significant comorbidity between TLE and MDD; however, the shared molecular mechanisms underlying this relationship remain unclear. This study aims to explore the common key genes associated with TLE and MD Read More
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Evaluating the Anti-inflammatory Efficacy of a Novel Bipyrazole Derivative in Alleviating Symptoms of Experimental Colitis
AimsThis aims to assess the efficacy of 2', 3, 3, 5'-Tetramethyl-4'-nitro-2'H-1, 3'-bipyrazole (TMNB), a novel compound, in colitis treatment.BackgroundInflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with limited effective treatments available. The exploration of new therapeutic agents is critical for advancing treatment options.ObjectiveTo assess the effect Read More
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Aloperine Alleviates Atherosclerosis by Inhibiting NLRP3 Inflammasome Activation in Macrophages and ApoE-/- Mice
Authors: Zengxu Wang, Yuchuan Wang, Faisal Raza, Hajra Zafar, Chunling Guo, Weihua Sui, Yongchao Yang, Ran Li, Yifen Fang and Bao LiBackground and Aims Atherosclerosis is a chronic cardiovascular disease which is regarded as one of the most common causes of death in the elderly. Recent evidence has shown that atherosclerotic patients can benefit by targeting interleukin-1 beta (IL-1β). Aloperine (ALO) is an alkaloid which is mainly isolated from Sophora alopecuroides L. and has been recognized as an anti-inflammatory disease. Herein, the effect of Read More
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