Article
Medicine, Research & Experimental
Xudong Wang, Yanshi Li, Min Pan, Tao Lu, Min Wang, Zhihai Wang, Chuan Liu, Guohua Hu
Summary: This study explored the role of CEA family member 5 (CEACAM5) in head and neck squamous cell carcinoma (HNSCC). The results showed a close association between CEACAM5 levels and lymph node (LN) metastasis, and high CEACAM5 levels had a positive impact on clinical prognosis. Experimental findings demonstrated that CEACAM5 inhibited cell proliferation and migration, and promoted apoptosis to suppress LN metastasis. Therefore, CEACAM5 has potential as both a prognostic marker and a therapeutic target in HNSCC.
Article
Biochemistry & Molecular Biology
Maksim Kukushkin, Vladimir Novotortsev, Vadim Filatov, Yan Ivanenkov, Dmitry Skvortsov, Mark Veselov, Radik Shafikov, Anna Moiseeva, Nikolay Zyk, Alexander Majouga, Elena Beloglazkina
Summary: A series of novel dispirooxindole derivatives containing S, O, and Se were synthesized and showed good cytotoxicity and selectivity towards colorectal carcinoma cells. Computational study suggested MDM2/p53 interaction as a possible target, but in vitro experiments did not observe significant p53 activation within a relevant concentration range.
Article
Chemistry, Medicinal
Shuai Wang, Fen-Er Chen
Summary: Inhibition of the MDM2-p53 protein-protein interaction using small-molecule inhibitors is a promising strategy for cancer therapy. Many highly potent and selective small-molecule MDM2 inhibitors have been discovered and are currently undergoing different clinical trials. This review provides an overview of the function of MDM2 and the identification, optimization, preclinical, and clinical studies of clinical-stage MDM2 inhibitors. It also discusses challenges, potential toxicity, and future perspectives, which will guide the design of new small-molecule MDM2 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jing Zhao, Alan Blayney, Xiaorong Liu, Lauren Gandy, Weihua Jin, Lufeng Yan, Jeung-Hoi Ha, Ashley J. Canning, Michael Connelly, Chao Yang, Xinyue Liu, Yuanyuan Xiao, Michael S. Cosgrove, Sozanne R. Solmaz, Yingkai Zhang, David Ban, Jianhan Chen, Stewart N. Loh, Chunyu Wang
Summary: Epigallocatechin gallate (EGCG) in green tea induces apoptosis in cancerous cells through a direct interaction with the tumor suppressor p53, inhibiting p53 ubiquitination by its regulatory E3 ligase MDM2 and stabilizing p53 for anti-tumor activity.
NATURE COMMUNICATIONS
(2021)
Article
Polymer Science
Jin Hau Lew, Omar K. Matar, Erich A. Mueller, Paul F. Luckham, Adrielle Sousa Santos, Maung Maung Myo Thant
Summary: In this study, the interaction between hydrolysed polyacrylamide (HPAM) with different molecular weights and calcium carbonate (CaCO3) was investigated using atomic force microscopy (AFM). The results showed that the presence of polymers, salt concentration, and molecular weight have significant effects on the interaction.
Article
Biochemistry & Molecular Biology
Gehad Lotfy, Yasmine M. Abdel Aziz, Mohamed M. Said, El Sayed H. El Ashry, El Sayed H. El Tamany, Marwa M. Abu-Serie, Mohamed Teleb, Alexander Domling, Assem Barakat
Summary: Combination of MDM2 and BCL2 inhibition can sensitize tumor cells and induce apoptosis synergistically. Novel MDM2 inhibitors 5i and 5q showed promising anticancer activities and apoptosis induction effects in cancer cells in vitro tests.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Dongjuan Si, Huijuan Luo, Xiaomeng Zhang, Kundi Yang, Hongmei Wen, Wei Li, Jian Liu
Summary: Inhibition of p53-MDM2 interactions is a promising strategy for cancer treatment. The unsaturated pyrrolidone compound 4h showed good binding affinity with MDM2 and demonstrated excellent antitumor activity by inducing cell cycle arrest and apoptosis. This compound has potential as a novel antitumor agent.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Akiko Fujimura, Hisashi Ishida, Tamiko Nozaki, Shuhei Terada, Yuto Azumaya, Tadashi Ishiguro, Yugo R. Kamimura, Tomoya Kujirai, Hitoshi Kurumizaka, Hidetoshi Kono, Kenzo Yamatsugu, Shigehiro A. Kawashima, Motomu Kanai
Summary: Peptides can be modified and used as ligands for targeting proteins of interest by inserting them into fusion proteins. This study demonstrates the use of a peptide ligand-inserted fusion protein as a universal adaptor for targeting proteins with cell-permeable and stable small molecules. By using specific small molecules, post-translational modifications can be targeted to specific residues on the proteins.
ACS CENTRAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Pankaj Attri, Hirofumi Kurita, Kazunori Koga, Masaharu Shiratani
Summary: This study investigated the impact of plasma treatment on Mdm2 and p53 through MD simulations, revealing that oxidized Mdm2 showed increased flexibility in bound or unbound states, potentially enhancing the availability of tumor suppressor protein p53 in plasma-treated cells. This insight into Mdm2 and p53 contributes to a better understanding of plasma oncology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Yuan Yin, Zhiyuan Jiang, Jiamei Fu, Yang Li, Chao Fang, Xiaonan Yin, Ye Chen, Na Chen, Junshu Li, Yanhong Ji, Xiaolan Su, Meng Qiu, Wei Huang, Bo Zhang, Hongxin Deng, Lei Dai
Summary: The study reveals the expression and function of SLC5 family members in colorectal cancer, showing that downregulation of SLC5A7 correlates with CRC staging and prognosis response. Overexpression of SLC5A7 inhibits CRC growth by promoting p53 protein expression, suggesting a potential therapeutic target for CRC.
Article
Chemistry, Medicinal
Gianni Chessari, Ian R. Hardcastle, Jong Sook Ahn, Burcu Anil, Elizabeth Anscombe, Ruth H. Bawn, Luke D. Bevan, Timothy J. Blackburn, Ildiko Buck, Celine Cano, Benoit Carbain, Juan Castro, Ben Cons, Sarah J. Cully, Jane A. Endicott, Lynsey Fazal, Bernard T. Golding, Roger J. Griffin, Karen Haggerty, Suzannah J. Harnor, Keisha Hearn, Stephen Hobson, Rhian S. Holvey, Steven Howard, Claire E. Jennings, Christopher N. Johnson, John Lunec, Duncan C. Miller, David R. Newell, Martin E. M. Noble, Judith Reeks, Charlotte H. Revill, Christiane Riedinger, Jeffrey D. St Denis, Emiliano Tamanini, Huw Thomas, Neil T. Thompson, Mladen Vinkovic, Stephen R. Wedge, Pamela A. Williams, Nicola E. Wilsher, Bian Zhang, Yan Zhao
Summary: In this study, novel isoindolinone-based MDM2 inhibitors were designed with rational structure guidance and showed potent inhibition of MDM2-p53 interaction, leading to cytostasis in an osteosarcoma xenograft model. These findings highlight the potential of targeting MDM2 in cancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Jingyuan Nie, Yibing Deng, Fang Tian, Shengchao Shi, Peng Zheng
Summary: Cation-pi interaction plays a crucial role in biological systems but its experimental verification and quantification at the molecular level are limited. In this study, atomic force microscopy-based single-molecule force spectroscopy was used to measure the stability and kinetics of NGAL protein with cation-pi interactions. The results demonstrated the high-precision detection of weak cation-pi interaction in NGAL.
Article
Chemistry, Multidisciplinary
Timothy Brown, Philip James Blowey, Jack Henry, Adam Sweetman
Summary: The acquisition of dense, three-dimensional, force fields with intramolecular resolution via noncontact atomic force microscopy (NC-AFM) has significantly advanced our understanding of molecular and two-dimensional materials on an atomic scale. Previous intramolecular force mapping was limited to cryogenic temperatures, but this study demonstrates high-resolution, three-dimensional force mapping of a single organic molecule at room temperature by using semiconducting materials to inhibit molecular diffusion and creating robust tip apexes, along with feedforward correction to overcome thermal drift challenges. The results obtained are comparable to those acquired at low temperature, enabling quantitative analysis of the adsorption-induced changes in molecular geometry at the picometer level.
Article
Biochemistry & Molecular Biology
Manuel Fuentes, Sanjeeva Srivastava, Angela M. Gronenborn, Joshua LaBaer
Summary: Understanding transient protein interactions at the proteome scale is a challenge. This study developed a novel label-free platform by combining nucleic acid programmable protein arrays (NAPPA) with surface plasmon resonance imaging (SPRi) to measure real-time protein interactions and determine affinity and rate constants. The technique was successfully applied to study the interactions between clinical mutants of p53 and its regulator MDM2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Siyu Zhang, Yifan Wang, Yujie Sun, Guangjian Zhao, Juan Wang, Lu Liu, Fang Liu, Peng Wang, Jinbo Yang, Ximing Xu
Summary: This study identified Hinokiflavone as a potential MDM2 inhibitor that suppresses mdm2 mRNA synthesis, leading to increased p53 protein expression and activation of the p53 pathway, ultimately reducing the survival rate of colon cells through cell cycle arrest and apoptosis induction.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Maria Anele Romeo, Maria Saveria Gilardini Montani, Rossella Benedetti, Andrea Arena, Gabriella D'Orazi, Mara Cirone
Summary: The combination of HDAC inhibitors and PARP inhibitors may improve the treatment of pancreatic cancer, which is a highly aggressive and therapy-resistant cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Roberta Gonnella, Luisa Guttieri, Maria Saveria Gilardini Montani, Roberta Santarelli, Erica Bassetti, Gabriella D'Orazi, Mara Cirone
Summary: Zinc supplementation enhances the sensitivity of lymphoma cells to radiation and increases cytotoxicity by exacerbating endoplasmic reticulum stress and activating pro-death function. This provides evidence for the use of zinc to reduce radiation doses in lymphoma cell treatment.
Review
Biochemistry & Molecular Biology
Mara Cirone, Gabriella D'Orazi
Summary: Expanding the understanding of the molecular mechanisms in tumor development, especially the interaction between oncogenic pathways, may lead to improved personalized cancer therapies. Nuclear factor erythroid 2-related factor 2 (NRF2) is crucial in cancer progression, not only due to its antioxidant activity but also its cross-talk with several oncogenic pathways. Additionally, NRF2's involvement in gammaherpesvirus-driven carcinogenesis is intriguing, as these viruses utilize the NRF2 pathway to protect tumor cells and avoid excessive reactive oxygen species levels. Manipulating the NRF2 pathway at different stages of gammaherpesvirus-mediated carcinogenesis may have varying outcomes, making it a potential target for cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Valerio Da Ros, Letizia Oddo, Yosra Toumia, Eugenia Guida, Silvia Minosse, Lidia Strigari, Silvia Strolin, Giulia Paolani, Francesca Di Giuliano, Roberto Floris, Francesco Garaci, Susanna Dolci, Gaio Paradossi, Fabio Domenici
Summary: This proof-of-concept study establishes a delivery strategy for radioactive lanthanides against recurrent glioblastoma using biocompatible PVA microbubbles and endovascular radiopharmaceutical infusion. The successful formulation turns PVA microbubbles into a microdevice with efficient Yttrium cargo loading. The selective targeting of Yttrium-loaded microbubbles on glioblastoma-associated tumor endothelial cells is achieved through biorecognition between overexpressed alpha(V)beta(3) integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) on the microbubble surface.
Review
Oncology
Alessia Garufi, Valerio D'Orazi, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Summary: Dysregulated angiogenesis is a common feature of cancer and other chronic inflammatory diseases. HIPK2, a protein that regulates multiple molecular pathways, has been found to play a role in angiogenesis and may serve as a potential biomarker for angiogenic diseases.
Review
Oncology
Alessia Garufi, Valerio D'Orazi, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Summary: HIPK2 is a protein kinase that plays a crucial role in various cellular functions and molecular pathways. It is involved in cancer cell response to cytotoxic drugs, regulation of fibrosis, angiogenesis, and neurological diseases. Recent studies have found that HIPK2 activity can be influenced by hyperglycemia, affecting cancer cell response to chemotherapy and the progression of diabetes complications.
Review
Oncology
Alessia Garufi, Giuseppa Pistritto, Gabriella D'Orazi
Summary: Fibrosis is a global medical problem that affects almost every organ and can lead to organ failure. The lack of effective biomarkers hampers the development of targeted therapies for fibrosis. Recent studies have highlighted the role of HIPK2 in regulating fibrosis, offering new possibilities for therapeutic intervention.
Editorial Material
Biochemistry & Molecular Biology
Gabriella D'Orazi
Article
Plant Sciences
Ilaria Borromeo, Fabio Domenici, Maddalena Del Gallo, Cinzia Forni
Summary: Plants irrigated with saline solutions undergo osmotic and oxidative stresses, affecting their growth, photosynthetic activity, and yield. Strategies such as seed priming and acclimation can improve plant tolerance to stress conditions. This study evaluated the combined effect of priming and acclimation on salt stress response of a salt-sensitive tomato cultivar.
Article
Biochemistry & Molecular Biology
Alessia Garufi, Riccardo Pettinari, Fabio Marchetti, Mara Cirone, Gabriella D'Orazi
Summary: Organometallic ruthenium (Ru)(II)-cymene complexes have potential pharmacological properties as alternative therapeutic agents. Polyphenols, such as curcumin and curcuminoids, also display beneficial properties in medicine, including chemoprevention. This study investigated the anticancer effect of a cationic Ruthenium (Ru)(II)-cymene Bisdemethoxycurcumin (Ru-bdcurc) complex, revealing that targeting the interconnection between the endoplasmic reticulum (ER)-resident chaperone GRP78/BiP and NRF2 pathways enhances the cytotoxic effect of Ru-bdcurc on colon cancer cells.
Article
Biochemistry & Molecular Biology
Gaio Paradossi, Rachel Grossman, Francesco Riccitelli, Federica Todaro, Zvi Ram, Sara Schioppa, Fabio Domenici
Summary: Researchers have developed injectable poly(vinyl alcohol) echogenic microbubbles (MBs) that can actively target tumor tissues by attaching a ligand with the tripeptide sequence RGD on their surface. The findings demonstrate that RGD-MBs have high adhesion to HUVEC cells and successfully bind to the drug TMZ. These improved PVA-MBs possess adhesion ability, cytotoxicity on glioblastoma cells, and support imaging.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Andrea Arena, Michele Di Crosta, Roberta Gonnella, Roberta Zarrella, Maria Anele Romeo, Rossella Benedetti, Maria Saveria Gilardini Montani, Roberta Santarelli, Gabriella D'Orazi, Mara Cirone
Summary: NFE2L2 and STAT3 are pro-survival molecules involved in the pathogenesis of PEL. Their simultaneous inhibition impairs the survival of PEL cells by regulating multiple pro-survival pathways. This study suggests that targeting NFE2L2 and STAT3 may be a potential therapeutic strategy for PEL, which has poor response to chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Oncology
Gabriella D'Orazi
Article
Chemistry, Multidisciplinary
Raffaella Salerno, Biagio Pede, Matteo Mastellone, Valerio Serpente, Veronica Valentini, Alessandro Bellucci, Daniele M. Trucchi, Fabio Domenici, Massimo Tomellini, Riccardo Polini
Summary: We have conducted an experimental study on the etching of detonation nanodiamond (DND) seeds during microwave chemical vapor deposition (MWCVD) conditions. This study is important for the formation of ultra-thin diamond films and various technological applications. The kinetics of seed disappearance were explained using a model based on the effect of particle size on the chemical potential of carbon atoms in DND and the activation energy of the reaction with atomic hydrogen. The model allowed for the estimation of rate coefficients for growth and etching.
Article
Polymer Science
Leonardo Severini, Alessia D'Andrea, Martina Redi, Sultan B. Dabagov, Valeria Guglielmotti, Dariush Hampai, Laura Micheli, Rocco Cancelliere, Fabio Domenici, Claudia Mazzuca, Gaio Paradossi, Antonio Palleschi
Summary: One of the main challenges in restoring cultural heritage through chemistry is finding greener and more effective methods for wet cleaning paper artifacts. In this study, a biocompatible method using ultrasound and polyvinyl alcohol microbubbles was proposed for wet cleaning paper. The method was tested on old and new papers using various analytical techniques, which confirmed its efficacy in removing cellulose degradation byproducts without causing thermal or mechanical damage to the paper. This method offers a solution to improve the readability of artifacts while minimizing the risk of ink diffusion.