Article
Oncology
Pawel Rogala, Anna M. Czarnecka, Bozena Cybulska-Stopa, Krzysztof Ostaszewski, Karolina Piejko, Marcin Zietek, Robert Dziura, Ewa Rutkowska, Lukasz Galus, Natasza Kempa-Kaminska, Joanna Seredynska, Wieslaw Bal, Katarzyna Kozak, Anna Surus-Hyla, Tomasz Kubiatowski, Grazyna Kaminska-Winciorek, Rafal Suwinski, Jacek Mackiewicz, Piotr Rutkowski
Summary: This study aimed to evaluate the association between different genotypes of human papillomavirus (HPV) and the risk of cervical cancer in Sichuan province, China.
Article
Biochemistry & Molecular Biology
William M. Marsiglia, Arthur Chow, Zaigham M. Khan, Liu He, Arvin C. Dar
Summary: This study presents a NanoBRET-based assay to quantify the direct target engagement of MEK inhibitors on MEK1 and its complexes with ARAF, BRAF, CRAF, KSR1 and KSR2 in living cells. The study reveals the preferences of MEK inhibitors among these complexes and their binding profiles. Furthermore, the assay can also report on the effect of pathogenic mutations on MEK inhibitor binding. These methods are important for screening compounds targeting specific complexes in the RAS-MAPK cascade.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Bohui Li, Xiangjun Kong, Harm Post, Linsey Raaijmakers, Daniel S. Peeper, Maarten Altelaar
Summary: Acquired resistance to MAPK inhibitors can limit the clinical efficacy in melanoma treatment. Research shows that in some cases, BRAF inhibitor-resistant melanoma cells can develop a dependency on the therapeutic drugs they are resistant to, offering a new approach for cancer treatment strategies.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Multidisciplinary Sciences
Gonzalo L. Gonzalez-Del Pino, Kunhua Li, Eunyoung Park, Anna M. Schmoker, Byung Hak Ha, Michael J. Eck
Summary: The dysregulation of the RAF/MEK/ERK pathway is associated with many cancers, making the proteins involved, like MEK, a focus of drug discovery efforts. Allosteric MEK inhibitors have complex effects on this pathway and are used in combination with BRAF inhibitors in malignant melanoma. Recent studies suggest that these inhibitors act most potently on BRAF/MEK complexes rather than on free active MEK.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Ashwin K. Chetty, Byung Hak Ha, Titus J. Boggon
Summary: This review focuses on the signaling pathways mediated by Rho family small GTPases and the specific roles of type II PAKs. The selectivity of Rho GTPases for PAK family members and the molecular basis for substrate recognition and regulation of signaling are discussed. The cross talk between Rho family small GTPases and the involvement of PAKs in diseases are also addressed.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Naryan Rustgi, Ann Maria, Nicolas Toumbacaris, Huiyong Zhao, Katherine Kargus, Morgan Bryant, Alexandra Waksmundzki, Ilinca Aricescu, Robert A. Lefkowitz, Bob T. Li, Joanne Chou, Marinela Capanu, Elisa de Stanchina, Sandra Misale, Jinru Shia, Rona Yaeger
Summary: This study aimed to explore the efficacy of combination therapy with RAF and MEK inhibitors for non-V600 BRAF-mutant tumors. The results showed that RAF inhibitors modestly inhibited signaling and growth in preclinical models of activated non-V600 BRAF mutations and allowed for a higher dose of MEK/ERK inhibitors. However, in a clinical trial, the combination treatment did not sufficiently inhibit the growth of these tumors.
Article
Oncology
Pui-Kei Wu, Seung-Keun Hong, Jong-In Park
Summary: The study found that RNA interference of mortalin can induce cell death in vemurafenib-resistant B-Raf mutant melanoma cells, and chemical inhibition of MEK1/2 and ERK1/2 can suppress mortalin depletion-induced death. Therefore, mortalin may serve as a potential therapeutic target for BRAFi-resistant BRAF mutant tumors.
Article
Oncology
Aayoung Hong, Marco Piva, Sixue Liu, Willy Hugo, Shirley H. Lomeli, Vincent Zoete, Christopher E. Randolph, Zhentao Yang, Yan Wang, Jordan J. Lee, Skylar J. Lo, Lu Sun, Agustin Vega-Crespo, Alejandro J. Garcia, David B. Shackelford, Steven M. Dubinett, Philip O. Scumpia, Stephanie D. Byrum, Alan J. Tackett, Timothy R. Donahue, Olivier Michielin, Sheri L. Holmen, Antoni Ribas, Gatien Moriceau, Roger S. Lo
Summary: Combining type II RAF inhibitor with MEK inhibitor effectively prevents and overcomes acquired resistance in cancers with specific mutations, while also expanding memory and activated CD8(+) T cells. This combination therapy shows potential in broad cancer indications and may be further enhanced by exploring mechanisms of MAPK protein interactions and preserving tumor-infiltrating T cells.
Article
Biochemistry & Molecular Biology
Chuwei Lin, Aneirin Alan Lott, Wei Zhu, Craig P. Dufresne, Sixue Chen
Summary: This study used metabolomics and proteomics to investigate the metabolites and protein profiles of the mpk4 mutant and the wild type plants. It revealed the involvement of MPK4 in polyamine synthesis and photosynthesis, providing insights into the metabolic networks potentially regulated by MPK4.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Dentistry, Oral Surgery & Medicine
Pattanin Montreekachon, Nopphanai Chaichana, Anupong Makeudom, Varunee Kerdvongbundit, Warisara Krisanaprakornkit, Suttichai Krisanaprakornkit
Summary: The study found that treatment with non-toxic doses of cannabidiol promotes proliferation and migration of human gingival fibroblasts. This effect may be achieved through the activation of the p38 MAPK and ERK1/2 signaling pathways.
JOURNAL OF PERIODONTAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Enkhtuya Radnaa, Lauren Richardson, Brett Goldman, Jared K. Burks, Tuvshintugs Baljinnyam, Natasha Vora, Hui-Juan Zhang, Elizabeth A. Bonney, Arum Han, Ramkumar Menon
Summary: This study investigated the impact of oxidative stress on p38 MAPK signaling and cell fate, using amnion epithelial cells. The results showed that excessive activation of p38 can have adverse effects on cell behavior and tissue homeostasis.
Article
Biochemistry & Molecular Biology
Wen-Yang Hu, Parivash Afradiasbagharani, Ranli Lu, Lifeng Liu, Lynn A. Birch, Gail S. Prins
Summary: The MEK/ERK and Rho/Rho kinase signaling pathways play crucial roles in prostate growth and branching during development, with MLCK-regulated MLC-P potentially serving as a central downstream target of both pathways in regulating prostate morphogenesis. Experiments demonstrated that inhibiting these pathways significantly inhibited prostate growth and blocked branching morphogenesis, highlighting their importance in prostate development.
Article
Oncology
Elizabeth I. I. Buchbinder, Anita Giobbie-Hurder, Patrick A. A. Ott
Summary: Adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Although the study provided preliminary evidence of safety and efficacy, it was terminated early due to the cessation of MCS110 development.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Biochemistry & Molecular Biology
Qianqian Xu, Peiyu Zhang, Xiaoyan Han, Huwei Ren, Weiyue Yu, Wei Hao, Bowen Luo, Muhammad Imran Khan, Ni Chen
Summary: This study investigates the pivotal role of Nuclear factor-erythroid 2-related factor 2 (NRF2) in the activation of DNA damage repair in lung cancer cells after x-rays exposure. The study shows that NRF2 knockdown disrupts damaged DNA repair and homologous recombination, and NRF2 activation mediates DNA damage response via the MAPK pathway. These findings suggest that NRF2 plays a critical role in the development of radioresistance, which is of great significance for the development of radiotherapies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Oncology
Yafei Zhou, Ying Xie, Tao Li, Peng Zhang, Tangting Chen, Zhongcai Fan, Xiaoqiu Tan
Summary: This study demonstrates that PAK1 is involved in AngII-induced proliferation, migration and transdifferentiation of cardiac fibroblasts through the JNK/c-Jun pathway.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Sotirios P. Fortis, Anthimia Batrinou, Hara T. Georgatzakou, Ioannis Tsamesidis, Grigorios Alvanidis, Effie G. Papageorgiou, Kontantinos Stamoulis, Dimitrios Gkiliopoulos, Georgia K. Pouroutzidou, Anna Theocharidou, Eleana Kontonasaki, Anastasios G. Kriebardis
Summary: This study evaluated the compatibility of human blood cells with silica-based mesoporous nanomaterials (MSNs) manufactured using the solgel method, with Ca and Ce as doping elements. The results showed that these nanomaterials had no impact on the viability of lymphocytes and monocytes, but reduced the viability of granulocytes. Additionally, the expression of Pselectin in platelets and the level of internal reactive oxygen species increased when exposed to MSNs. The presence of Ce in the MSNs improved their hemocompatibility to some extent. Further research is needed to understand how MSNs may affect different blood components and design safe and effective MSNs for biomedical applications.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Retraction
Biochemistry & Molecular Biology
Tiechao Jiang, Dongli Jiang, Dong You, Lirong Zhang, Long Liu, Qini Zhao
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Yuting Chen, Lin Chen, Shiheng Zhu, Hui Yang, Zhongming Ye, Huanhuan Wang, Haipeng Wu, Yao Wu, Qian Sun, Xiaoshan Liu, Hairong Liang, Huanwen Tang
Summary: This study investigates the impact of exosomal derived miR-1246 from HQ-transformed cells on cell-to-cell communication in recipient TK6 cells. The results show that exosomal miR-1246 targets CCNG2, regulating TK6 cell cycle arrest, highlighting its potential as a biomarker for HQ-induced malignant transformation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuping Yu, Yaming Mu, Kai Wang, Ling Wang, Chunying Wang, Zexin Yang, Yu Liu, Shuxian Li, Meihua Zhang
Summary: Fetal growth restriction (FGR) is a common complication in obstetrics, and its exact cause is unknown. In this study, we constructed 1-NP exposed pregnant mice models and found that 1-NP induced FGR. Additionally, we observed significant ferroptosis in placental trophoblasts from 1-NP exposed mice and human FGR patients. Using in vitro cell models, we demonstrated that 1-NP impaired trophoblast biological function and induced cellular ferroptosis. We also identified the ERK signaling pathway and CYP1B1 as key regulators of 1-NP-induced ferroptosis. This study provides new insights into the aetiology of FGR and the reproductive toxicity of environmental pollutants.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Lei Hou, Yingying Zhao, Shiyu Zhao, Xuexia Zhang, Xia Yao, Jianjun Yang, Ziteng Wang, Shuaibing Liu
Summary: This study systematically characterized the UGTs enzymes involved in the formation of M4 and the inhibitory effects of ciprofol and its metabolite M4 on P450s enzymes. In vitro-in vivo extrapolation and PBPK simulations were performed to predict potential drug-drug interactions caused by ciprofol.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Review
Biochemistry & Molecular Biology
Disheng Liu, Lu Wang, Wuhua Ha, Kan Li, Rong Shen, Degui Wang
Summary: Renal fibrosis is a common outcome of renal injuries, characterized by structural destruction and functional decline of the kidneys. Hypoxia induces the activation of HIF-1 alpha, which regulates cellular metabolism, proliferation, apoptosis, and inflammation, contributing to the development of renal fibrosis. Understanding the regulation and cascade reactions mediated by HIF-1 alpha can provide new insights for studying the mechanism of renal fibrosis.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Zhao-Bo Luo, Liu-Hui Yang, Sheng-Zhong Han, Shuang-Yan Chang, Hongye Liu, Zhi-Yong An, Xiu-Li Zhang, Biao-Hu Quan, Xi-Jun Yin, Jin-Dan Kang
Summary: This study demonstrates that cyclophosphamide (CTX) treatment has detrimental effects on oocytes and embryos, leading to DNA damage, apoptosis, and abnormal histone modification. Supplementation with LBH589 can effectively restore the developmental potential of embryos by increasing histone modification levels and restoring protein expression of NF-kappa B, a key regulator of early embryo development.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Sheng Chen, Hanqing Xu, Yi He, Chen Meng, Yunhui Fan, Yunkun Qu, Yingguang Wang, Wei Zhou, Xiaojian Huang, Hongbo You
Summary: Osteoarthritis is a heterogeneous disease that affects the entire joint. This study found that Carveol can reverse the inflammatory state of macrophages, promote their anti-inflammatory effects, and protect cartilage by activating the NRF2/HO-1/NQO1 pathway and reducing ROS clearance. The results also showed that Carveol can alleviate the pathological changes of osteoarthritis in mice, suggesting its potential therapeutic efficacy.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Liyi Wei, Tingting Wang, Mingcui Luo, Shuai Zhang, Mengxi Lu, Xinli Zhou, Xuelei Cheng, Hui Wang, Dan Xu
Summary: This study found that azithromycin during pregnancy may have toxic effects on fetal hippocampal development, especially in the late pregnancy, high dose, and multi-course situation. The results also suggest that the SOX2/Wnt signaling pathway may be involved in this toxicity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Review
Biochemistry & Molecular Biology
Di Wu, Faheem Ahmed Khan, Kejia Zhang, Nuruliarizki Shinta Pandupuspitasari, Windu Negara, Kaifeng Guan, Fei Sun, Chunjie Huang
Summary: Retinoic acid (RA) is a signaling molecule derived from vitamin A/retinol, with implications in various aspects of health and disease. It regulates cell functioning through both transcriptional and non-genomic mechanisms, influencing cell-fate determination, neurogenesis, visual function, inflammatory responses, and gametogenesis commitment.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Review
Biochemistry & Molecular Biology
Bilal Murtaza, Lili Wang, Xiaoyu Li, Muhammad Yasir Nawaz, Muhammad Kashif Saleemi, Aisha Khatoon, Xu Yongping
Summary: Mycotoxins in food pose significant concerns for food safety and public health, potentially causing a range of adverse symptoms and cancer development. Deoxynivalenol (DON) is particularly worrisome due to its harm to vital organs. Altered mycotoxins present possible risks to the environment and well-being, necessitating further research into their adverse consequences. Accurately assessing the risk posed by modified mycotoxins remains challenging.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Emine Toraman, Buesra Budak, Cemil Bayram, Selma Sezen, Behzad Mokhtare, Ahmet Hacimueftueoglu
Summary: The study suggests that parthenolide (PTL) may have therapeutic effects in treating testicular toxicity caused by paclitaxel (PTX) through reducing oxidative stress and increasing glutathione levels. PTL also promotes the expression of genes involved in reproduction and sperm production.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Correction
Biochemistry & Molecular Biology
Cuicui Zhuang, Hui Huo, Wanfa Fu, Wanyue Huang, Lulu Han, Miao Song, Yanfei Li
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Taotao Zhao, Jia Lv, Mingyuan Peng, Jiahui Mi, Shaosan Zhang, Jie Liu, Tong Chen, Zilong Sun, Ruiyan Niu
Summary: This study explores the protective effects of fecal microbiota transplantation (FMT) and short-chain fatty acids (SCFAs) supplementation on learning and memory impairment caused by fluoride exposure in mice. The results show that FMT and SCFAs can improve memory deficits and alleviate pathological damages caused by fluoride, possibly by activating the BDNF-PI3K/AKT pathway. Furthermore, the disordered gut microbiome caused by fluoride can be restored through frequent FMT.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Biochemistry & Molecular Biology
Yong Liu, Zhaofei Pang, Yadong Wang, Jichang Liu, Guanghui Wang, Jiajun Du
Summary: This study reveals that silencing PKD2 promotes ferroptosis in LUAD by increasing reactive oxygen species, malondialdehyde accumulation, intracellular iron content and cell death. Overexpression of PKD2 prevents autophagic degradation of ferritin and promotes proliferation, migration and invasion of LUAD cells. Moreover, targeting PKD2 enhances the efficacy of carboplatin through ferroptosis and apoptosis in LUAD.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)