Review
Oncology
Caroline Molinaro, Alain Martoriati, Katia Cailliau
Summary: Cells respond to genotoxic stress through complex protein pathways called DNA damage response (DDR), ensuring genomic integrity and activating processes like DNA repair, cell cycle regulation, and programmed cell death. Alterations in DDR network proteins can lead to various diseases, including cancer. Recent technological advancements have allowed for the exploitation of DDR vulnerabilities to improve cancer treatments through DNA damage strategies and combination therapies.
Review
Oncology
Ying Zhang, Yumin Wu, Jun Wu, Chen Wu
Summary: This review discusses the anti-tumor activity of HIPEC against primary malignancies and peritoneal metastases, as well as its advantages and limitations in treatment. It also analyzes the biological and immunological anticancer mechanisms of HIPEC, as well as its potential combination with other therapies.
Article
Biochemistry & Molecular Biology
Chao Dong, Liwei An, Cheng-han Yu, Michael S. Y. Huen
Summary: The DYRK1B kinase plays a crucial role in maintaining rDNA stability, nucleolar reorganization, and inhibition of rRNA synthesis. Inhibition of DYRK1B results in sustained nucleolar transcription, hypersensitivity to DSBs at rDNA arrays, and requirement for DSB repair and rDNA copy number maintenance. These findings highlight the importance of DYRK1B as a key signaling intermediate in coordinating DSB repair and rDNA transcriptional activities within the nucleolus.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sabrina X. Van Ravenstein, Kavi P. Mehta, Tamar Kavlashvili, Jo Ann W. Byl, Runxiang Zhao, Neil Osheroff, David Cortez, James M. Dewar
Summary: Using Xenopus egg extracts, this study demonstrates that the TOP2 poisons etoposide and doxorubicin inhibit DNA replication through different mechanisms. Etoposide induces TOP2-dependent DNA breaks and TOP2-dependent fork stalling, while doxorubicin stalls replication forks independently of TOP2 by intercalating into parental DNA.
Review
Neurosciences
Vanessa Brinkmann, Gerhard Fritz
Summary: This article provides an overview of the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN) and suggests that DNA damage-related stress responses could be potential targets for prevention. Additionally, the use of the nematode Caenorhabditis elegans as a model organism is discussed for further investigation of CIPN mechanisms and identification of protective compounds.
Article
Multidisciplinary Sciences
Makoto Isono, Kazuki Okubo, Takako Asano, Akinori Sato
Summary: Combining MK-8776 with gemcitabine inhibits viability and colony formation of bladder cancer cells, induces apoptosis, and suppresses tumor growth in vivo. The combination treatment elevates gamma H2A.X and suppresses Rad51 expression, suggesting CHK1 inhibition combined with gemcitabine as a potential therapeutic strategy for bladder cancer.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Sophie Gilbert, Benjamin Peant, Anne-Marie Mes-Masson, Fred Saad
Summary: Inhibition of IKK-epsilon expression or using IKK-epsilon inhibitors can decrease proliferation and tumor volume of castrate resistant prostate cancer cells. Moreover, these inhibitors can induce senescence, DNA damage, and genomic instability. Combining Amlexanox and Olaparib can enhance the anti-cancer effects.
Article
Pharmacology & Pharmacy
Amr Ahmed WalyEldeen, Haidan M. El-Shorbagy, Hamdi M. Hassaneen, Ismail A. Abdelhamid, Salwa Sabet, Sherif Abdelaziz Ibrahim
Summary: This study evaluated the in vivo anticancer activity of a synthetic isoquinoline chalcone (CHE) in mice with solid carcinoma. The results showed that CHE treatment significantly inhibited tumor growth and induced apoptosis through oxidative stress and DNA damage. Additionally, CHE exhibited minimal toxicity on the liver and kidney.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
C. Fritsch, J-F Gout, S. Haroon, A. Towheed, C. Chung, J. LaGosh, E. McGann, X. Zhang, Y. Song, S. Simpson, P. S. Danthi, B. A. Benayoun, D. Wallace, K. Thomas, M. Lynch, M. Vermulst
Summary: Research shows that mutagenic compounds not only cause genetic mutations, but are also a powerful source of transcription errors. These errors occur in both dividing and nondividing cells, and sometimes greatly exceed the number of mutations in the genome. Additionally, DNA repair is crucial in mitigating transcriptional mutagenesis after exposure to mutagens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Dongxiao Zhang, Danni Zhong, Jiang Ouyang, Jian He, Yuchen Qi, Wei Chen, Xingcai Zhang, Wei Tao, Min Zhou
Summary: In this study, researchers have successfully developed an oral delivery system using Spirulina platensis as a microcarrier to protect the whole small intestine from radiation-induced injury during radiotherapy. The system accumulates the drug effectively and provides superior radioprotection compared to free drug and enteric capsules, preventing radiation-induced intestinal injury without affecting tumor regression. It also has benefits on gut microbiota homeostasis and long-term safety.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Mateusz Kciuk, Adrianna Gielecinska, Somdutt Mujwar, Damian Kolat, Zaneta Kaluzinska-Kolat, Ismail Celik, Renata Kontek
Summary: Doxorubicin (DOX) is a key component in current anti-cancer treatment regimens, but its precise mechanisms of action remain unclear. Recent evidence suggests that DOX exhibits pleiotropic anticancer activity, including DNA damage, reactive oxygen species (ROS) production, apoptosis, senescence, autophagy, ferroptosis, and pyroptosis induction, as well as immunomodulation. This review aims to gather information on the anticancer mechanisms of DOX and its impact on the anti-tumor immune response, providing a rationale for the importance of DOX in modern cancer therapy.
Article
Biochemistry & Molecular Biology
Joanna Drogosz-Stachowicz, Katarzyna Gach-Janczak, Marek Mirowski, Jacek Pietrzak, Tomasz Janecki, Anna Janecka
Summary: The antitumor activity of a synthetic analog, AJ-418, with a 5,8-quinolinedione scaffold was investigated on breast cancer cell lines. AJ-418 showed strong antiproliferative activity against MCF-7 and MDA-MB-231 cells with lower cytotoxicity towards healthy MCF-10A cells. The compound induced morphological changes and apoptosis in cancer cells, while remaining unaffected in non-tumorigenic cells.
Article
Medical Laboratory Technology
Liu Dong, Haoqin Jiang, Zhihua Kang, Ming Guan
Summary: Drugs targeting DNA repair have rapidly developed in cancer therapy, with numerous inhibitors being used in preclinical and clinical stages. Biomarkers are crucial for predicting chemotherapy response and DNA mismatch repair (MMR) pathway plays a significant role in cancer occurrence and development. This review provides a concise introduction of MMR genes and focuses on potential biomarkers for therapeutic response and resistance, aiming to clarify the controversial and contradictory results regarding the underlying mechanisms.
CLINICA CHIMICA ACTA
(2023)
Article
Nanoscience & Nanotechnology
Yi Lu, Die Jia, Xianbin Ma, Mengyun Liang, Shengxin Hou, Wei Qiu, Yuan Gao, Peng Xue, Yuejun Kang, Zhigang Xu
Summary: A stimuli-responsive prodrug nanogel was developed using a two-in-one cross-linking strategy to deliver a combination of chemotherapeutic drugs for improving the deficiencies of chemotherapy and enhancing cancer therapeutic efficiency. The high drug loading capacity and suitable nanoscale size of the obtained nanogel facilitate cell uptake and tumor penetration, leading to enhanced tumor growth inhibition by the synergistic DNA damage in response to the reductive tumor microenvironment. This unique prodrug nanogel shows promise as a candidate for effective tumor treatment-based chemotherapy.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Chemistry, Inorganic & Nuclear
Xuling Xue, Ying Fu, Liang He, Luca Salassa, Ling-Feng He, Yuan-Yuan Hao, Madeleine J. Koh, Clement Soulie, Russell J. Needham, Abraha Habtemariam, Claudio Garino, Kirill A. Lomachenko, Zhi Su, Yong Qian, Martin J. Paterson, Zong-Wan Mao, Hong-Ke Liu, Peter J. Sadler
Summary: Half-sandwich Os-arene complexes exhibit promising anticancer activity, especially the OsCUR-2 complex, which shows remarkable photocytotoxicity towards a range of cancer cell lines and has the potential for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT). The photochemistry of these complexes involves selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) under blue light or UVA excitation.
INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kirill A. Konovalov, Wei Wang, Guo Wang, Eshani C. Goonetilleke, Xin Gao, Dong Wang, Xuhui Huang
Summary: Epigenetic modification 5-carboxycytosine (5caC) in the genome can induce transcription pauses by impacting the translocation process of Pol II.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ilona Christy Unarta, Siqin Cao, Shintaroh Kubo, Wei Wang, Peter Pak-Hang Cheung, Xin Gao, Shoji Takada, Xuhui Huang
Summary: The study elucidated the dynamics of Thermus aquaticus holoenzyme's gate opening using a quasi-Markov State Model, revealing the differential roles of beta-lobe and clamp in DNA loading and the mechanism by which Myxopyronin inhibits clamp opening. Additionally, a critical role of beta-lobe in DNA loading was uncovered, presenting an opportunity for the development of antibiotics targeting this region of RNAP. The study also demonstrated the potential of quasi-Markov State Models in studying biomolecular dynamics based on generalized master equation formalism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Physical
Hanlin Gu, Wei Wang, Siqin Cao, Ilona Christy Unarta, Yuan Yao, Fu Kit Sheong, Xuhui Huang
Summary: The paper presents a new method based on RPnet to cluster microstates into macrostates for analyzing the conformational dynamics of biological macromolecules. Through the reverse-projection scheme and neural network, successful analysis of dynamics of 2D potential, alanine dipeptide, and RNA polymerase was achieved.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Physical
Siqin Cao, Yunrui Qiu, Ilona C. Unarta, Eshani C. Goonetilleke, Xuhui Huang
Summary: The 3D reference interaction site model with Ion-Dipole Correction (3DRISM-IDC) is proposed to accurately predict the water distributions around negatively charged solute molecules. It significantly outperforms the existing 3DRISM theory in accurately predicting solvation structures and improving the accuracy of hydration free-energy calculation. The 3DRISM-IDC theory shows promise in studying solvation properties for nucleic acids and other biomolecules containing negatively charged functional groups.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Materials Science, Multidisciplinary
Bojun Liu, Yunrui Qiu, Eshani C. Goonetilleke, Xuhui Huang
Summary: Self-assembly is a powerful approach for fabricating advanced materials, but understanding its kinetics at a molecular level is challenging. Kinetic network models based on molecular dynamics simulations have shown potential in elucidating self-assembly pathways. This article discusses challenges in using these models and reviews the recent development of machine learning approaches to address them. It also highlights the potential of these models in molecular self-assembly studies and material design.
Review
Biochemistry & Molecular Biology
Ilona Christy Unarta, Eshani C. Goonetilleke, Dong Wang, Xuhui Huang
Summary: RNA polymerase II (Pol II) incorporates complementary ribonucleotides into the growing RNA chain one at a time and ensures transcriptional fidelity by backtracking and cleaving misincorporated nucleotides. Recent studies have made progress in understanding the catalytic mechanisms of Pol II, including the two-metal-ion mechanism for nucleotide addition and the role of Pol II residues in facilitating the catalysis. Interestingly, Pol II relies on its residues to recognize misincorporated nucleotides during backtracking before cleavage, effectively compartmentalizing its dual catalytic functions using the same active site.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Kirill A. Konovalov, Cheng-Guo Wu, Yunrui Qiu, Vijaya Kumar Balakrishnan, Pankaj Singh Parihar, Michael S. O'Connor, Yongna Xing, Xuhui Huang
Summary: Mutations in protein phosphatase 2A (PP2A) disrupt its autoinhibition and phosphorylation-induced activation, leading to intellectual disability and cancer. Allosteric pathway analysis and biochemical experiments reveal that the disease mutant E198K weakens the stabilizing pathways of the regulatory subunit B56d, while the mutant E200K induces exposure of the active site. Remarkably, the allosteric pathways of E198K resemble those in phosphorylation-activated WT, suggesting a conserved mechanism for alleviating autoinhibition.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Siqin Cao, Michael L. L. Kalin, Xuhui Huang
Summary: Integral equation theory (IET) is an effective solvation model that provides computational efficiency and accuracy. We have developed a new software package called EPISOL, which utilizes 3D-RISM calculations to obtain solvation structure and free energies of solute molecules in different solvents. EPISOL features various closures, free energy functionals, and numerical schemes to enhance stability and convergence. It is compatible with AMBER and GROMACS simulation packages and can efficiently handle large biomolecules. EPISOL is a valuable tool for calculating solvation density distributions and solvent free energy in chemical and biological systems.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Anthony J. Dominic III, Siqin Cao, Andres Montoya-Castillo, Xuhui Huang
Summary: Conformational changes in biomolecular systems are essential for their function and understanding these changes can have significant implications for drug discovery and bioengineering applications. While Markov state models have provided insights into slow conformational dynamics, this Perspective highlights the importance of incorporating memory effects to improve computational efficiency and accuracy. Various techniques such as Fokker-Planck equations, recurrent neural networks, and generalized master equations, which consider memory effects, are discussed in this article.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Eric M. M. Kohn, Kirill Konovalov, Christian A. A. Gomez, Gillian N. N. Hoover, Andrew Kai-hei Yik, Xuhui Huang, Jeffrey D. D. Martell
Summary: This study demonstrates the utility of terminal alkynes in improving the binding properties of DNA aptamers to proteins. The terminal alkyne enhances the binding affinity by stabilizing the aptamer-protein interface through noncovalent interactions. This is the first case of terminal alkynes enhancing the binding properties of an aptamer.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Physical
Siqin Cao, Yunrui Qiu, Michael L. Kalin, Xuhui Huang
Summary: The generalized master equation (GME) is a powerful method for studying biomolecular dynamics. We present a new method, the Integrative GME (IGME), which analytically solves the GME when the memory kernels have decayed to zero, overcoming the challenges of the quasi Markov State Model (qMSM).
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Bojun Liu, Mingyi Xue, Yunrui Qiu, Kirill A. Konovalov, Michael S. O'Connor, Xuhui Huang
Summary: Identifying slow collective variables (CVs) in self-assembly dynamics is challenging due to permutation and rotational symmetries as well as the out-of-equilibrium nature. In this study, GraphVAMPnets, a combination of graph neural networks and variational Markovian process theory, is utilized to overcome these challenges and identify the slow CVs in self-assembly processes of two systems. The method proves effective in capturing the essential dynamics of self-assembly.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Yunrui Qiu, Michael S. O'Connor, Mingyi Xue, Bojun Liu, Xuhui Huang
Summary: Conformational changes are crucial in chemical and biological processes, but analyzing complex conformational changes can be challenging due to the vast number of kinetic pathways involved. To address this issue, researchers have developed a path classification algorithm (LPC) that efficiently groups parallel kinetic pathways into distinct metastable path channels, making them easier to comprehend.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Multidisciplinary
Kirill A. Konovalov, Ilona Christy Unarta, Siqin Cao, Eshani C. Goonetilleke, Xuhui Huang
Summary: Markov state models (MSMs) are commonly used for studying protein folding, but their application to functional conformational changes is limited. To address the challenge of slow dynamics in functional conformational changes, automatic feature selection methods and dimensionality reduction techniques are recommended, with the use of quasi-MSMs (qMSMs) suggested to reduce state numbers for easier interpretation.
Article
Chemistry, Physical
Congmin Yuan, Eshani C. Goonetilleke, Ilona Christy Unarta, Xuhui Huang
Summary: The ongoing pandemic caused by SARS-CoV-2 highlights the need for effective therapeutics. Inhibition of SARS-CoV-2 RdRp by nucleotide analogs offers a promising antiviral strategy. Research on 2'-modified nucleotides shows varying inhibitory effects on SARS-CoV-2 RdRp, which could potentially aid in the rational design of antiviral agents.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)