Article
Environmental Sciences
Cao Zhaohui, Tang Cifei, Huang Di, Zeng Weijia, Han Cairui, Li Zecong, Hu Xiaobo
Summary: In this study, it was found that cadmium exposure induced cell death in HepG2 cells via a ROS-mediated PERK-CHOP-related apoptotic signaling pathway, providing a novel insight into the mechanisms of cadmium-induced hepatotoxicity. Inhibitors targeting oxidative stress and ER stress might be potential strategies for preventing or treating this disorder.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhaolin Gao, Min Li, Fei Yao, Xiaobo Xia, Tianqi Duan, Jingzhuo Meng, Yanxia Huang, Ye He, Adonira Saro, Jufang Huang
Summary: The study investigated the effects and underlying mechanisms of valdecoxib on retinal ischemia-reperfusion injury and oxygen-glucose deprivation/recovery injury. The results showed that valdecoxib protected R28 cells by reducing cell apoptosis and exerted a protective effect on retinas by inhibiting retinal ganglion cell apoptosis. In addition, valdecoxib reversed the expression of certain proteins induced by glaucomatous model and the reversal was mediated by the PERK-ATF4-CHOP pathway. These findings suggest that valdecoxib protects against glaucomatous injury by inhibiting ER stress-induced apoptosis via the PERK-ATF4-CHOP pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhaohui Cao, Zhuan Wu, Tingting Duan, Cifei Tang, Di Huang, Xiaobo Hu
Summary: This study found that curcumin improves oxidative stress-induced apoptosis in pancreatic beta cells by inhibiting the PERK-CHOP pathway of ER stress. Curcumin acts by activating SIRT1 expression and reducing the expression of CHOP. These findings suggest that curcumin and SIRT1 may serve as a potential therapeutic approach for T1DM.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Qiuya Wu, Duanfang Zhou, Zhengze Shen, Bo Chen, Gang Wang, Lihong Wu, Limei Zhang, Xiaoli Li, Lie Yuan, Yuanli Wu, Na Qu, Weiying Zhou
Summary: VPS34-IN1 is a specific selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K) and has been shown to exhibit a significant antitumor effect in leukemia and liver cancer. In this study, the researchers focused on the anticancer effect and potential mechanism of VPS34-IN1 in estrogen receptor positive (ER+ ) breast cancer. The results showed that VPS34-IN1 inhibited the viability of ER+ breast cancer cells by inducing apoptosis through the activation of the PERK/ATF4/CHOP pathway of ER stress. These findings provide new insights and potential treatment strategies for ER+ breast cancer.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jonathan Turpin, Daed El-Safadi, Gregorie Lebeau, Etienne Frumence, Philippe Despres, Wildriss Viranaicken, Pascale Krejbich-Trotot
Summary: Zika virus manipulates cellular responses to delay apoptosis and optimize virus production; by impairing the expression of CHOP/DDIT3 at a translational level, ZIKV inhibits ER stress-driven apoptosis; ZIKV relies on cellular machinery and the unfolded protein response to complete its viral cycle, posing a threat to human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mini Jeong, Jong-Il Shin, Jaewook Cho, Yong-Joon Jeon, Jin-Hyun Kim, Jeehee Youn, Kyungho Lee
Summary: In this study, the pro-apoptotic effects of docosahexaenoic acid (DHA) in human fibroblast-like synovial cells from rheumatoid arthritis (RA) patients were investigated. The results showed that DHA treatment induced caspase-8-dependent apoptosis in a dose-dependent manner and reduced the TNF-alpha-mediated induction of MMP-9 and IL-1 beta. DHA also induced ER stress and upregulated the expression of death receptor 5 (DR5) through the activation of CHOP. These findings suggest that DHA can induce apoptosis in RA-FLSs through the upregulation of DR5 via the activation of CHOP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Jingmin Che, Huanhuan Lv, Jiancheng Yang, Bin Zhao, Sibo Zhou, Tongyao Yu, Peng Shang
Summary: In this study, iron overload induced apoptosis in osteoblasts through activating ER stress, resulting in mitochondrial dysfunction. Pretreatment with NAC or TUDC attenuated cell apoptosis and restored protein expression related to iron metabolism.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Yu Wu, Xiaomei Fan, Sha Chen, Ling Deng, Lu Jiang, Shaonan Yang, Zhi Dong
Summary: The aim of this study was to investigate the protective mechanism of geraniol against cerebral ischemia-reperfusion injury (CIRI). The results showed that geraniol effectively attenuated cerebral infarction and pathological injury, reduced ER-stress-related protein expression and apoptosis occurrence, and increased anti-apoptotic protein expression, suggesting a protective effect against CIRI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sun-Ji Park, Yeawon Kim, Chuang Li, Junwoo Suh, Jothilingam Sivapackiam, Tassia M. Goncalves, George Jarad, Guoyan Zhao, Fumihiko Urano, Vijay Sharma, Ying Maggie Chen
Summary: Albuminuria is not only a symptom but also a cause of glomerular disease, leading to glomerulosclerosis and interstitial fibrosis. The study identifies CHOP and TXNIP as critical molecular linkers in albuminuria-induced kidney injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Fang Fang, Pingting Liu, Haoliang Huang, Xue Feng, Liang Li, Yang Sun, Randal J. Kaufman, Yang Hu
Summary: Endoplasmic reticulum (ER) stress is found to be associated with various neurodegenerative diseases. In this study, it is shown that deletion of CHOP and/or its upstream regulator ATF4 in retinal ganglion cells (RGCs) promotes RGC and optic nerve (ON) survival and preserves visual function in mouse glaucoma models. These findings suggest that blocking the neuronal intrinsic ATF4/CHOP axis of ER stress is a promising neuroprotection strategy for neurodegeneration.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Chemistry, Multidisciplinary
Xiao-xuan Yu, Meng-yuan Zhu, Jia-rong Wang, Hui Li, Po Hu, Ying-jie Qing, Xiang-yuan Wang, Hong-zheng Wang, Zhan-yu Wang, Jing-yan Xu, Qing-long Guo, Hui Hui
Summary: The study shows that LW-213 effectively inhibits the growth of CTCL cells and induces apoptosis. The mechanisms involve ROS formation, calcium release, and activation of different signaling pathways.
ACTA PHARMACOLOGICA SINICA
(2021)
Review
Biochemistry & Molecular Biology
James M. Pemberton, Justin P. Pogmore, David W. Andrews
Summary: Axonal degeneration and neuronal cell death are regulated by BCL-2 family proteins, with potential influences from other cell death pathways. Deciphering the subsets of proteins required and separately regulating these outcomes is essential for future research and pharmacological interventions.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Taewoo Kim, Seong-Gyu Ko
Summary: JI017 is a potent anti-cancer drug for ovarian cancer treatment, mediating endoplasmic reticulum stress and apoptosis through the Nox4-PERK-CHOP signaling pathway. Combination treatment with radiation can overcome radioresistance in ovarian cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Fenglei Chen, Jiarong Sun, Yujing Wang, Jason William Grunberger, Zhen Zheng, Nitish Khurana, Xianyu Xu, Xin Zhou, Hamidreza Ghandehari, Jinlong Zhang
Summary: This study reveals the mechanisms of silica nanoparticles (SNPs) inducing follicular atresia and apoptosis in granulosa cells. SNPs are found to increase calcium ion concentration in the cytoplasm and activate endoplasmic reticulum (ER) stress. The PERK-ATF4-CHOP-ERO1 alpha pathway plays an essential role in SNP-induced ovarian toxicity, leading to apoptosis via IP3R1-mediated calcium mobilization.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lina Y. Hassab, Samah S. Abbas, Reham A. Mohammed, Dalaal M. Abdallah
Summary: This study aimed to investigate the effects of DMF treatment on Huntington's disease (HD). The results showed that DMF improved motor deficits, increased striatal dopamine content, and reduced astrogliosis in HD rats. Mechanistically, DMF suppressed endoplasmic reticulum stress, inhibited apoptotic pathway, enhanced antioxidant capacity, and activated AKT/mTOR and BDNF/TrkB/AKT/CREB signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
