Journal of exploratory research in pharmacology最新文献_第8页

PINK1 Deficiency Aggravates the β-amyloid-attenuated Mitophagy-lysosomal Degradation in PC12 Cells PINK1缺乏加剧了PC12细胞中β-淀粉样蛋白减毒的自噬-溶酶体降解

Journal of exploratory research in pharmacology Pub Date : 2022-01-11 DOI: 10.14218/jerp.2021.00053

Xiao-Juan Wang, Yong-Qiang Xue, He-Ling Zhang, Ying Yu, Peng Liu

{"title":"PINK1 Deficiency Aggravates the β-amyloid-attenuated Mitophagy-lysosomal Degradation in PC12 Cells","authors":"Xiao-Juan Wang, Yong-Qiang Xue, He-Ling Zhang, Ying Yu, Peng Liu","doi":"10.14218/jerp.2021.00053","DOIUrl":"https://doi.org/10.14218/jerp.2021.00053","url":null,"abstract":"<abstract><sec>\u0000<title>Background and objectives</title>\u0000PTEN-induced putative kinase 1 (PINK1) is a mitochondrial kinase that regulates mitophagy. PINK1-deficient mAPP mice display low LC3B levels, and PINK1 overexpression enhances autophagy and increases the expression level of lysosome-associated membrane protein 1 (LAMP1). The present study evaluated whether altered PINK1 expression could modulate β-amyloid (Aβ)-treated mitophagy in PC12 cells, a simple cellular model to simulate pathological changes in neurodegenerative diseases in vitro.\u0000</sec><sec>\u0000<title>Methods</title>\u0000PC12 cells were transfected with PINK1 siRNA for 48 h, and then incubated with 20 μM Aβ25–35 for 24 h. The relevant protein expression was determined by immunofluorescence, immunoelectron microscopy, and Western blot. Mitochondrial membrane potential (MMP) was tested by JC-1-based confocal fluorescent imaging.\u0000</sec><sec>\u0000<title>Results</title>\u0000Following Aβ25–35 treatment, PINK1 silencing significantly decreased the levels of LC3B, Parkin, and LAMP1 as well as Parkin in mitochondria, p62 degradation, but increased OPTN and Parkin expression in PC12 cells, relative to that of the control PC12 cells. Furthermore, PINK1 silencing decreased MMP in PC12 cells.\u0000</sec><sec>\u0000<title>Conclusion</title>\u0000PINK1 deficiency deteriorated the blockade of the Aβ25–35-induced mitophagy-lysosome pathway in PC12 cells. Aβ-treated PC12 cells might be a valuable cellular model to evaluate PINK1-mediated mitophagy and bioactive compound screening.\u0000</sec></abstract>\u0000","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138527492","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}

引用次数: 0

Potential SARS-CoV-2 Spike Protein-ACE2 Interface Inhibitors: Repurposing FDA-approved Drugs 潜在的SARS-CoV-2刺突蛋白- ace2界面抑制剂:重新利用fda批准的药物

Journal of exploratory research in pharmacology Pub Date : 2022-01-01 DOI: 10.14218/jerp.2021.00050

V. Kouznetsova, Aidan Zhang, Mark A Miller, M. Tatineni, J. Greenberg, I. Tsigelny

引用次数: 2

Traditional Herbal Medicines in Mood Disorders: A Promising Development Target 传统草药治疗情绪障碍:一个有前途的发展目标

Journal of exploratory research in pharmacology Pub Date : 2021-12-10 DOI: 10.14218/jerp.2021.00046

Zhi-hui Zhang, Zeng‐bo Ding, X. Wu, Ke Wang, Su-Xia Li, Wei‐li Zhu

引用次数: 0

Subclinical Hyperthyroidism is One of the Modifiable Risk Factors for Atrial Fibrillation 亚临床甲状腺功能亢进是心房颤动的可改变危险因素之一

Journal of exploratory research in pharmacology Pub Date : 2021-12-09 DOI: 10.14218/jerp.2021.00054

M. Stojanović, Vidosav Stojanović, Duska C. Stojanovic

引用次数: 0

Porphyromonas Gingivalis in the Pathogenesis of Alzheimer’s Disease and Its Therapeutic Target 牙龈卟啉单胞菌在阿尔茨海默病发病机制中的作用及其治疗靶点

Journal of exploratory research in pharmacology Pub Date : 2021-12-02 DOI: 10.14218/jerp.2021.00030

Tom Seymour, Jinwei Zhang

{"title":"Porphyromonas Gingivalis in the Pathogenesis of Alzheimer’s Disease and Its Therapeutic Target","authors":"Tom Seymour, Jinwei Zhang","doi":"10.14218/jerp.2021.00030","DOIUrl":"https://doi.org/10.14218/jerp.2021.00030","url":null,"abstract":"The leading cause of dementia is Alzheimer’s disease (AD), which affects millions worldwide. Aging populations can foretell the worsening burden of the disease in the future. AD is characterised by the following hallmark pathologies: amyloid-β over-production and deposition, abnormal hyperphosphorylation of tau leading to the formation of neurofibrillary tangles, and neuroinflammation. Many potential treatments fail in clinical trials, suggesting that present theories are outdated or lead to therapeutic dead-ends. A gum disease-causing species of bacteria, Porphyromonas gingivalis, is being increasingly linked with AD, given the ubiquity of gum disease amongst older populations, and studies have revealed that the bacteria causes and exacerbates AD pathology both in vitro and in vivo. P. gingivalis produce many neurotoxic molecules, including gingipain enzymes, lipopolysaccharide and phosphoglycerol dihydroceramides, and all of these have been shown to affect AD pathologies. Numerous mechanisms by which these neurotoxic species reach the brain have been proposed, and one of these is the bacteria’s use of outer membrane vesicles. This review presents the present evidence of the effects of P. gingivalis and its outer membrane vesicles, gingipains, lipopolysaccharide and phosphoglycerol dihydroceramides, on neurodegeneration in neuronal cultures, mice models and post-mortem studies, and determines how this evidence can be used to develop new treatments for AD.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45792026","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}

引用次数: 3

Potential SARS-CoV-2 Nonstructural Protein 15 Inhibitors: Repurposing FDA-Approved Drugs 潜在的SARS-CoV-2非结构蛋白15抑制剂:重新利用fda批准的药物

Journal of exploratory research in pharmacology Pub Date : 2021-10-14 DOI: 10.14218/jerp.2021.00032

Jason Y Tang,Igor F. Tsigelny,Jerry P. Greenberg,Mark A. Miller,Valentina L. Kouznetsova

引用次数: 0

Generic Solving of One-compartment Toxicokinetic Models 单室毒性动力学模型的通用求解

Journal of exploratory research in pharmacology Pub Date : 2021-09-30 DOI: 10.14218/jerp.2021.00024

Sandrine Charles,Aude Ratier,Christelle Lopes

引用次数: 0

Treatment with Gaoziban Tablet Ameliorates Depression by Promoting GSK-3β Phosphorylation to Enhance the Wnt/β-catenin Activation in the Hippocampus of Rats 高子板片通过促进GSK-3β磷酸化增强大鼠海马Wnt/β-catenin激活改善抑郁症

Journal of exploratory research in pharmacology Pub Date : 2021-09-09 DOI: 10.14218/jerp.2021.00016

Xin Zou, Hailong Yin, Lei Shi, Hai-ping Li, Mengheng Wang, Wanci Song, Yang Luo, Wei-Liang Chen, Hezhen Wu, Yan-fang Yang, Junfeng Zan, Yan-wen Liu, Hanxiong Dan, Q. Yin, Pengtao You

引用次数: 0

Potential SARS-CoV-2 Nonstructural Protein 15 (NSP15) Inhibitors: Repurposing FDA-Approved Drugs 潜在的严重急性呼吸系统综合征冠状病毒2型非结构蛋白15（NSP15）抑制剂：重新利用美国食品药品监督管理局批准的药物

Journal of exploratory research in pharmacology Pub Date : 2021-08-11 DOI: 10.33774/chemrxiv-2021-ht9sx

Jason X Tang, I. Tsigelny, J. Greenberg, Mark R. Miller, V. Kouznetsova

{"title":"Potential SARS-CoV-2 Nonstructural Protein 15 (NSP15) Inhibitors: Repurposing FDA-Approved Drugs","authors":"Jason X Tang, I. Tsigelny, J. Greenberg, Mark R. Miller, V. Kouznetsova","doi":"10.33774/chemrxiv-2021-ht9sx","DOIUrl":"https://doi.org/10.33774/chemrxiv-2021-ht9sx","url":null,"abstract":"Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths worldwide, pushing the urgent need for an efficient treatment. Nonstructural protein 15 (NSP15) is a promising target due to its importance for SARS-CoV-2’s evasion of the host’s innate immune response. Methods: Using the crystal structure of SARS-CoV-2 NSP15 endoribonuclease, we developed a pharmacophore model of the functional centers in the NSP15 inhibitor’s binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. The conformations of these compounds underwent 3D fingerprint similarity clustering, and possible conformers were docked to the NSP15 binding pocket. We also simulated docking of random compounds to the NSP15 binding pocket for comparison. Results: This search identified 170 compounds as potential inhibitors of SARS-CoV-2 NSP15. The mean free energy of docking for the group of potential inhibitors were significantly lower than for the group of random compounds. Twenty-one of the compounds identified as potential NSP15 inhibitors were antiviral compounds used in the inhibition of a range of viruses, including MERS, SARS-CoV, and even SARS-CoV-2. Eight of the selected antiviral compounds in cluster A are pyrimidine analogues, six of which are currently used in a clinical setting. Four tyrosine kinase inhibitors were identified with potential SARS-CoV-2 inhibition, which is consistent with previous studies showing some kinase inhibitors acting as antiviral drugs. Conclusions: We recommended testing of these 21 selected antiviral compounds for the treatment of COVID-19.","PeriodicalId":73746,"journal":{"name":"Journal of exploratory research in pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47004033","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}

引用次数: 1

Network Pharmacology Elucidates the Anti-Inflammatory Mechanisms of QingFeiPaiDu Decoction for Treatment of COVID-19 网络药理学研究清肺排毒汤治疗COVID-19的抗炎机制

Journal of exploratory research in pharmacology Pub Date : 2021-07-30 DOI: 10.14218/jerp.2021.00011

Yan Liu, L. Xiong, Yanyu Wang, Maohui Luo, Longfei Zhang, Yongqing Zhang

引用次数: 0