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Pharmacology & Pharmacy
Oisin N. Kavanagh, Shayon Bhattacharya, Luke Marchetti, Robert Elmes, Finbarr O'Sullivan, John P. Farragher, Shane Robinson, Damien Thompson, Gavin M. Walker
Summary: Drug-mediated correction of abnormal biological zinc homeostasis is important for treating neurodegeneration, cancer, and viral infections. Our study provides evidence that hydroxychloroquine, a potential treatment for COVID-19, does not bind and transport zinc through ionophoric mechanisms as previously claimed.
Article
Biochemistry & Molecular Biology
Huiling Gao, Hehong Sun, Nan Yan, Pu Zhao, He Xu, Wei Zheng, Xiaoyu Zhang, Tao Wang, Chuang Guo, Manli Zhong
Summary: Zinc homeostasis imbalance is a major cause of Parkinson's disease, and ATP13A2 plays an important role in regulating zinc homeostasis and alpha-synuclein accumulation. High zinc ion treatment leads to reduced spatial exploration behavior in mice, increased phosphorylation levels of alpha-synuclein, inhibition of the autophagy pathway, and activation of apoptosis signaling pathways. Overexpression of ATP13A2 reverses these protein changes, while its knockout exacerbates alpha-synuclein phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Isadora Carolina Betim Pavan, Fernanda Luisa Basei, Matheus Brandemarte Severino, Ivan Rosa e Silva, Luidy Kazuo Issayama, Mariana Camargo Silva Mancini, Mariana Marcela Gois, Luiz Guilherme Salvino da Silva, Rosangela Maria Neves Bezerra, Fernando Moreira Simabuco, Jorg Kobarg
Summary: NEK6 is a central kinase in developing castration-resistant prostate cancer (CRPC), but the pathways it regulates are unclear. This study found that knocking out NEK6 decreased cell viability, mitochondrial activity, and antioxidant defenses, while increasing intracellular ROS levels, JNK phosphorylation, and DNA damage markers. Exogenous overexpression of NEK6 had the opposite effects. NEK6 also played a role in cell death, cisplatin sensitivity, and nuclear localization of NF-kappa B2. These findings suggest that NEK6 inhibition may be a new therapeutic strategy for CRPC.
Article
Chemistry, Inorganic & Nuclear
Liyan Wang, Xicheng Liu, Yuting Wu, Xian He, Xiaohui Guo, Wenshan Gao, Lin Tan, Xiang-Ai Yuan, Jinfeng Liu, Zhe Liu
Summary: This paper investigates the potential value of half-sandwich iridium(III) complexes with favorable luminescence performance in the anticancer field. Ten fluorescent complexes were prepared and showed potential antiproliferative activity, with Ir6 exhibiting the best activity and excellent fluorescence performance. Ir6 followed an energy-dependent cellular uptake mechanism, specifically accumulating in mitochondria and inducing mitochondrial-mediated apoptosis. It also arrested the cell cycle, catalyzed NADH oxidation, reduced the mitochondrial membrane potential, induced an increase in ROS level, and exhibited an oxidation mechanism. In vivo antitumor assay confirmed that Ir6 effectively inhibited tumor growth and was safer than cisplatin.
INORGANIC CHEMISTRY
(2023)
Article
Neurosciences
Margaux Teil, Evelyne Doudnikoff, Marie-Laure Thiolat, Sylvain Bohic, Erwan Bezard, Benjamin Dehay
Summary: The study investigated the effects of zinc modulation on the progression of Parkinson's disease, and found that pharmacological chelation of zinc can attenuate PD-related pathological changes and dopaminergic neuronal degeneration, suggesting zinc chelation as a potential disease-modifying strategy for treating PD.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Marziyeh Shalchi Tousi, Houri Sepehri, Sepideh Khoee, Mahdi Moridi Farimani, Ladan Delphi, Fariba Mansourizadeh
Summary: The study evaluated the potential of iron oxide nanoparticles coated with mPEG-b-PLGA as a carrier to enhance the therapeutic efficacy of eupatorin in prostate cancer cells. Results showed successful encapsulation of eupatorin in nanoparticles, leading to significant inhibition of cell growth and induction of apoptosis.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Article
Chemistry, Medicinal
Chris Yap, Jennifer L. Short, Joseph A. Nicolazzo
Summary: The study demonstrated that clioquinol can increase the abundance and function of breast cancer resistance protein at the blood-brain barrier, potentially impacting the levels of drugs and endogenous substrates in the brain.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Oisin Kavanagh, Robert Elmes, Finbarr O'Sullivan, John Farragher, Shane Robinson, Gavin Walker
Summary: The importance of zinc in biology has gained greater recognition recently due to its essential contributions to the function of many endogenous enzymes. However, little is known about the structure and function of zinc ionophores, despite the growth of knowledge and increased interest in zinc.
Article
Multidisciplinary Sciences
Xiwang Yang, Ya Wen, Shaomin Liu, Liqiang Duan, Tongfeng Liu, Zhou Tong, Zhuo Wang, Yinmin Gu, Yibo Xi, Xiaodong Wang, Dingsan Luo, Ruobing Zhang, Yajuan Liu, Yang Wang, Tianyou Cheng, Siyuan Jiang, Xiaofeng Zhu, Xiaohui Yang, Yongbo Pan, Shuwen Cheng, Qinong Ye, Jinfei Chen, Xiaoding Xu, Shan Gao
Summary: The study revealed the critical role of a long noncoding RNA LCDR in regulating lysosome function, which affects lung cancer cell survival. LCDR interacts with hnRNP K to maintain lysosomal membrane integrity, leading to lysosomal cell death and apoptosis. Targeting LCDR/hnRNP K/LAPTM5 axis may provide potential therapeutic targets for cancer treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Environmental Sciences
Xingyao Pei, Dingkuo Liu, Jianjun Li, Liuan Li, Xiangbin Ding, Wenjuan Zhang, Zibin Li, Gang Xu, Cun Li, Daowen Li
Summary: This study investigates the hepatotoxic mechanism of ZnO NPs and reveals the crosstalk between autophagy and pyroptosis. The findings suggest that autophagy serves as a protective response against pyroptosis induced by ZnO NPs, and the regulation of autophagy and lysosome by TFEB can alleviate the pyroptosis. This study provides new insights for the risk assessment and therapeutic strategy of ZnO NPs-induced pyroptosis.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Chemistry, Inorganic & Nuclear
P. K. Anuja, Nilmadhab Roy, Utpal Das, Seshu Varddhan, Suban K. Sahoo, Priyankar Paira
Summary: A class of half-sandwich [Ru(eta(6)-p-cymene)(N<^>O 8-hydroxyquinoline)(PTA)] complexes were introduced for brain cancer therapy, and their anticancer activities and toxic effects were evaluated through cellular, molecular, and in vivo experiments.
DALTON TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Kaili Du, Jiahui Shi, Shixue Cheng, Shuqi Hang, Zongxian Ding, Siyu Liu, Dan Li
Summary: 4-Hydroxynonenal (4-HNE), a toxic end-product of lipid peroxidation, is involved in various diseases. This study reveals that 4-HNE can activate transcriptional factor EB (TFEB), promoting autophagy and lysosomal function. TFEB plays a crucial role in the cellular response to 4-HNE-induced cell damage. Targeting TFEB to enhance autophagy and lysosomal function may offer a promising approach for treating diseases associated with 4-HNE accumulation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Qian-Wen Zhang, Mirza Muhammad Faran Ashraf Baig, Tian-Qi Zhang Ting-Ting Zhai Xia
Summary: This study developed a novel therapeutic strategy by incorporating valinomycin into liposomes, which can facilitate apoptosis pathway in cells and achieve significant inhibition of tumor growth in liver cancer.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Lili Qu, Bingqian Lin, Wenping Zeng, Chunhong Fan, Haotian Wu, Yushu Ge, Qianqian Li, Canjun Li, Yanan Wei, Jing Xin, Xingbing Wang, Dan Liu, Chunlei Cang
Summary: Lysosomal potassium channel TMEM175 is regulated by apoptotic regulator Bcl-2, and its modulation plays an important role in cellular processes and Parkinson's disease.
Article
Environmental Sciences
Yuan Liu, Yaxin Yao, Wenjing Tao, Feng Liu, Songbai Yang, Ayong Zhao, Dan Song, Xiangchen Li
Summary: This study investigated the role of CoQ10 in alleviating BPA-induced cell damage, demonstrating that CoQ10 effectively restored abnormalities caused by BPA, reduced apoptosis and ROS levels, improved mitochondrial membrane potential, and enhanced lysosome function and autophagy flux.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)