Review
Biochemistry & Molecular Biology
Jia-Bao Huang, Zhi-Ru Chen, Shu-Long Yang, Fen-Fang Hong
Summary: Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. Nitric oxide (NO) and nitric oxide synthases (NOS) play a significant role in the pathogenesis of RA by inducing inflammation and oxidative stress. Targeting NOS/NO signaling pathways may be an effective approach for managing RA, and there are several drugs currently in clinical trials that show promise in treating RA by modulating NOS/NO activity.
Review
Biochemistry & Molecular Biology
Gabriele Serreli, Monica Deiana
Summary: Nitric oxide (NO) is released in various organs and tissues and has important functions in organisms. There are three isoforms of the enzyme that produce NO, namely eNOS, iNOS, and nNOS. The expression and activity of these isoforms depend on different intracellular signaling pathways. Recent studies have focused on natural compounds like polyphenols, which can be obtained through diet, for their ability to modulate NOS isoforms' pathways. In this review, we aim to provide scientific evidence on the activity of dietary polyphenols in regulating NOS isoform expression and functionality.
Article
Cell Biology
Joon Sung Park, Jungyuen Choi, Longxing Cao, Jyotidarsini Mohanty, Yoshihisa Suzuki, Andy Park, David Baker, Joseph Schlessinger, Sangwon Lee
Summary: The mini-protein mb7 is found to bind with high affinity to the c-isoforms of FGFR, inhibiting cellular signaling induced by specific FGFs and blocking interaction between FGFR with Klotho proteins. This makes mb7 an antagonist of the metabolic hormones FGF19 and FGF21, providing insights and strategies for developing therapeutics for diseases caused by aberrantly activated FGFRs.
Article
Multidisciplinary Sciences
Eric M. Lynch, Michael A. DiMattia, Steven Albanese, Gydo C. P. van Zundert, Jesse M. Hansen, Joel D. Quispe, Madison A. Kennedy, Andreas Verras, Kenneth Borrelli, Angela Toms, Neelu Kaila, Kevin D. Kreutter, Joshua J. McElwee, Justin M. Kollman
Summary: CTPS1 is essential for an effective immune response, with deficiency leading to severe immunodeficiency. CTPS1 expression is up-regulated in activated lymphocytes to meet the increased demand for nucleic acid and lipid synthesis. Selective inhibition of CTPS1 could be beneficial for treating immune disorders and lymphocyte cancers, with recent small-molecule inhibitors showing promise in inhibiting proliferation of human T cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Engineering, Biomedical
Menghao Shi, Jiulong Zhang, Yu Wang, Chang Peng, Haiyang Hu, Mingxi Qiao, Xiuli Zhao
Summary: This study constructed acid-activated nanoparticles for the delivery of beta-lapachone, which demonstrated enhanced penetration capability through charge-reversal and size-reduction strategies. Reactive oxygen species and nitric oxide production from the nanoparticles effectively inhibited tumor metastasis and showed favorable antitumor efficacy.
Article
Chemistry, Multidisciplinary
Fang Yuan, Cuiling Zhang, Xianzhu Luo, Xiaokun Shen, Yuezhong Xian
Summary: ATP stimulus-responsive tetrahedral DNA-gated fluorescent covalent organic frameworks (COFs) were developed for estradiol (E2) delivery and controllable release. The fluorescent COFs with an efficient E2 loading showed great potential against myocardial ischemia and reperfusion injury.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Lan Jiang, Xue Zhang, Yuya Sato, Guoliang Zhu, Atsushi Minami, Weiyan Zhang, Taro Ozaki, Bin Zhu, Zhixin Wang, Xinye Wang, Kangjie Lv, Jingyu Zhang, Yongheng Wang, Shushan Gao, Chengwei Liu, Tom Hsiang, Lixin Zhang, Hideaki Oikawa, Xueting Liu
Summary: Two previously unreported fungal bifunctional terpene synthases, FoFS and AtAS, have been discovered in this study. FoFS catalyzes the formation of fusoxypenes A-C and (-)-astellatene, while AtAS synthesizes preaspterpenacid I. The enantioselective synthesis of sesterterpenes and the cyclization pathways of the fusoxypenes were also characterized.
Article
Neurosciences
David Perez-Boyero, Carlos Hernandez-Perez, Jorge Valero, Valeria Lorena Cabedo, Jose Ramon Alonso, David Diaz, Eduardo Weruaga
Summary: The main olfactory bulb (MOB) is a neural structure that processes olfactory information. Nitric oxide (NO), produced mainly by neuronal nitric oxide synthase (nNOS), plays a crucial role in the plasticity and functioning of the MOB. The absence of nNOS expression in nNOS-KO mice leads to a reduced olfactory capacity, while an increase in the expression of endothelial nitric oxide synthase (eNOS) is observed. However, the level of NO generated in the MOB does not appear to change significantly. These findings suggest that nNOS is essential for the proper functioning of the olfactory system.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Tijana Suboticki, Olivera Mitrovic Ajtic, Dragoslava Djikic, Marijana Kovacic, Juan F. Santibanez, Milica Tosic, Vladan P. Cokic
Summary: In various systems, hydroxyurea has been shown to stimulate the release of nitric oxide or activate nitric oxide synthase. Through inhibiting nitric oxide metabolites, hydroxyurea is able to inhibit the growth of mature erythroid colonies and impact the presence of iNOS immunoreactive CFU-E.
Article
Chemistry, Physical
Mengyu Sun, Yanjuan Sang, Qingqing Deng, Zhengwei Liu, Jinsong Ren, Xiaogang Qu
Summary: A nanozyme-based NO generator, cerium oxide (CeO2)-AT, has been developed to selectively produce nitric oxide (NO) in cancer cells for tumor treatment. The generator can disrupt the mitochondrial respiratory chain of tumor cells and induce cell apoptosis by catalyzing the production of NO in the mitochondria of cancer cells. Furthermore, the generator can improve the performance of NO gas therapy by catalyzing H2O2 to produce O-2. This study provides a new approach for safe and specific cancer therapy using highly selective NO-based treatment.
Article
Medical Laboratory Technology
Michael R. Miller, Stephen R. Koch, Hyehun Choi, Fred S. Lamb, Ryan J. Stark
Summary: This study found that ASK1 expression increased in sepsis and after LPS challenge, with ASK1 inhibitors reducing cytokine production but not affecting permeability. Physical interaction between eNOS and ASK1 was observed, and ASK1 inhibition mainly impaired JNK activation, affecting cytokine production.
TRANSLATIONAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Jing Yu, Chao Zhang, Chun Song
Summary: In the past few decades, the development of Hsp90 inhibitors for cancer treatment has been ongoing. However, many compounds evaluated in clinical trials were not approved by the FDA due to toxic effects and lack of efficacy. Insufficient isoform selectivity has been identified as one of the reasons for these failures. Therefore, the development of isoform-specific Hsp90 inhibitors could lead to significant progress in finding therapeutic agents for cancer and other diseases. This article provides a summary of classic pan-inhibitors of Hsp90 and discusses the design strategies used in drug discovery. It also summarizes current isoform-specific Hsp90 inhibitors, including their discovery processes and potential indications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Roman Roy, Joshua Wilcox, Andrew J. Webb, Kevin O'Gallagher
Summary: Nitric oxide (NO) plays important roles in regulating various functions in the cardiovascular system. Different isoforms of nitric oxide synthase (NOS) have distinct functions and localizations, and may have different pathophysiological roles. Modulating NOS activity is a potential therapeutic approach for cardiovascular diseases. This review summarizes recent advances in understanding the physiological role of NOS isoforms and discusses the possibility of targeting NO and NOS activity for novel cardiovascular therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Shixun Liu, Anming Xu, Bin Xie, Fengxue Xin, Weiliang Dong, Jie Zhou, Min Jiang
Summary: This study reveals the importance of c-di-GMP in coordinating the synthesis of biofilm exopolysaccharides and RLs in Pseudomonas aeruginosa. By comparing different strains and analyzing the genome, it is found that the regulation of c-di-GMP level is crucial for switching between these two synthesis processes.
Article
Chemistry, Multidisciplinary
Lingling Lv, Yaoqing Chu, Lianjiang Tan
Summary: Antibacterial RBS@Cu:ZnO nanoparticles were prepared by decorating Cu-doped ZnO nanoparticles with Roussin's black salt (RBS), which served as a nitric oxide (NO) precursor. The nanoparticles exhibited crystal morphology and nanoscaled sizes as confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) tests. The nanoparticles showed high antibacterial activity due to the synergistic effects of Cu-doped ZnO and released NO under visible laser irradiation. The antibacterial activity could be controlled by adjusting the power output of laser irradiation. The RBS@Cu:ZnO nanoparticles have potential applications in biomedicine and pharmaceutics as antibacterial agents.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Bohumir Gruner, Michael Kugler, Suzan El Anwar, Josef Holub, Jan Nekvinda, Dmytro Bavol, Zdenka Ruzickova, Klara Pospisilova, Milan Fabry, Vlastimil Kral, Jiri Brynda, Pavlina Rezacova
Summary: A series of derivatives based on cobalt bis(dicarbollide)(1-) anion were reported, which can inhibit CAIX with subnanomolar inhibition constants and high selectivity. The compound with n=3 and two substituents in a rac-arrangement showed the best inhibitory properties. X-ray crystallography was used to study the interactions of these compounds with the active site of CAIX on the structural level.
Review
Biochemistry & Molecular Biology
Zdenek Kejik, Robert Kaplanek, Michal Masarik, Petr Babula, Adam Matkowski, Petr Filipensky, Katerina Vesela, Jakub Gburek, David Sykora, Pavel Martasek, Milan Jakubek
Summary: Flavonoids, common plant natural products, can suppress ROS-related damage through chelation of transition metal ions, with iron being the most significant. Their interaction with Fe(II) and Fe(III) ions can significantly affect their biological properties. Special biological effects of their iron metallocomplexes, such as the inhibition of iron-containing enzymes, have been discussed in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Chemical
Milan Jakubek, Michal Masarik, Tomas Briza, Robert Kaplanek, Katerina Vesela, Nikita Abramenko, Pavel Martasek
Summary: The study found that some PPO herbicides showed significant inhibition of hPPO, while the newly synthesized compounds did not exhibit significant activity. However, a designed model based on determined IC50 values can better predict PPO herbicidal toxicity and improve the design of synthetic inhibitors.
Review
Biochemistry & Molecular Biology
Nikita Abramenko, Frederic Vellieux, Petra Tesarova, Zdenek Kejik, Robert Kaplanek, Lukas Lacina, Barbora Dvorankova, Daniel Rosel, Jan Brabek, Adam Tesar, Milan Jakubek, Karel Smetana
Summary: Estrogens may have a protective effect against COVID-19 by influencing the cardiovascular/pulmonary/immune system, reducing cytokine storms, and directly inhibiting viral replication. In addition to natural hormones, phytestrogens and synthetic molecules may also have anti-viral activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Anna Bogucka-Kocka, Przemyslaw Kolodziej, Anna Makuch-Kocka, Daria Rozycka, Sebastian Rykowski, Jan Nekvinda, Bohumir Gruner, Agnieszka B. Olejniczak
Summary: This study demonstrates the activity of a series of 1,8-naphthalimide-carborane/metallacarborane conjugates against Rhabditis sp. The conjugates with cobaltacarborane showed high activity compared to other carborane conjugates.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Suzan El Anwar, Lucia Pazderova, Dmytro Bavol, Mario Bakardjiev, Zdenka Ruzickova, Ondrej Horacek, Lukas Fojt, Radim Kucera, Bohumir Gruner
Summary: In this study, we have reported a difunctional modification method for anionic cobalta bis(dicarbollide)(1(-)) clusters by introducing a B(8,8')-oxygen bridging unit and organic alkylazide substituents on the carbon atoms of the metallacarborane cage, which enhances their structural rigidity. These ions show good binding motifs for incorporation into organic molecules through Huisgen-Sharpless (2+3) cycloaddition reactions, and can be separated into enantiomers using chiral stationary phases. The electrochemical testing results indicate that these compounds exhibit high peaks located outside the typical signals of biomolecules.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lukas Fojt, Bohumir Gruner, Jan Nekvinda, Ece Zeynep Tuzun, Ludek Havran, Miroslav Fojta
Summary: This study explores the effect of hydrophilic alkylhydroxy and carboxy groups on the electrochemical signals of cobalta bis(dicarbollide) ions in aqueous buffers. The results show that the location and type of substitution have minimal effect on the electrochemical response, but the intensity of the signals is dependent on concentration.
Article
Biochemistry & Molecular Biology
Veronika Antonyova, Zdenek Kejik, Tereza Brogyanyi, Robert Kaplanek, Katerina Vesela, Nikita Abramenko, Tomas Ocelka, Michal Masarik, Adam Matkowski, Jakub Gburek, Renata Abel, Andrean Goede, Robert Preissner, Petr Novotny, Milan Jakubek
Summary: Predicting and studying the effects of non-psychotropic cannabinoids on DNA methylation is crucial for assessing the safety of these products. Researchers found that these cannabinoids can interfere with TET enzymes, affecting methylation patterns, possibly through chelating ferrous ions.
BIOORGANIC CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Jindriska Leischner Fialova, Katerina Honigova, Martina Raudenska, Lucie Miksatkova, Renata Zobalova, Jiri Navratil, Jana Smigova, Taraka Ramji Moturu, Tomas Vicar, Jan Balvan, Katerina Vesela, Nikita Abramenko, Zdenek Kejik, Robert Kaplanek, Jaromir Gumulec, Daniel Rosel, Pavel Martasek, Jan Brabek, Milan Jakubek, Jiri Neuzil, Michal Masarik
Summary: Mitochondria play a crucial role in cellular growth and function, and recent studies have challenged the notion that they are not involved in cancer growth. This study shows that pentamethinium salts, originally designed as mitochondrial probes, have a strong inhibitory effect on cancer cell proliferation and migration by interfering with mitochondrial respiration and causing oxidative stress. These findings suggest that pentamethinium salts could be potential novel anti-cancer agents.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Tereza Brogyanyi, Robert Kaplanek, Zdenek Kejik, Bozena Hosnedlova, Veronika Antonyova, Nikita Abramenko, Katerina Vesela, Pavel Martasek, Martin Vokurka, Des R. Richardson, Milan Jakubek
Summary: This study tested novel iron chelators for their cytotoxicity against pancreatic cancer cells, showing high toxicity and selectivity. The mechanism of action of the chelators may be associated with mitophagy induction.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Veronika Antonyova, Ameneh Tatar, Tereza Brogyanyi, Zdenek Kejik, Robert Kaplanek, Frederic Vellieux, Nikita Abramenko, Alla Sinica, Jan Hajduch, Petr Novotny, Bettie Sue Masters, Pavel Martasek, Milan Jakubek
Summary: In this study, we synthesized a series of pyrrolopyrrole derivatives and found that the basic pyrrolo[3,2-b]pyrrole derivative 1 exhibited strong inhibitory activity against TET1 protein. Furthermore, derivative 1 showed potent anticancer activity and exclusive mitochondrial localization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Veronika Talianova, Zdenek Kejik, Robert Kaplanek, Katerina Vesela, Nikita Abramenko, Lukas Lacina, Karolina Strnadova, Barbora Dvorankova, Pavel Martasek, Michal Masarik, Magdalena Houdova Megova, Petr Busek, Jana Krizova, Lucie Zdrazilova, Hana Hansikova, Erik Vlcak, Vlada Filimonenko, Aleksi Sedo, Karel Smetana, Milan Jakubek
Summary: IL-6 signaling plays a crucial role in the pathogenesis of serious diseases such as chronic inflammation and cancer. Two newly designed bis-pentamethinium salts compounds showed potential in binding IL-6 receptor and inhibiting mitochondrial metabolism in cancer cells.
Article
Chemistry, Analytical
Ondrej Horacek, Lucie Novakova, Ece Tuzun, Bohumir Gruner, Frantisek Svec, Radim Kucera
Summary: The continuous expansion of research in the field of stable carboranes and their wide potential in drug design require fundamental studies on chiral separations. This study aimed to develop a straightforward method for chiral separations of racemic mixtures of anionic cluster carboranes and metallacarboranes. The results demonstrated the clear advantage of SFC over HPLC in terms of analysis time and variety of successfully separated compounds.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yao Chen, Andrea Barba-Bon, Bohumir Gruner, Mathias Winterhalter, M. Alphan Aksoyoglu, Sushil Pangeni, Maryam Ashjari, Klaudia Brix, Giulia Salluce, Yeray Folgar-Camean, Javier Montenegro, Werner M. Nau
Summary: Cobalt bisdicarbollides (COSANs) are used as selective and efficient molecular carriers to transport hydrophilic oligopeptides through membranes. They can permeate lipid bilayer membranes without causing membrane damage. COSANs transport arginine-rich and lysine-rich peptides effectively, but cannot transport small molecules or anionic cargos. The transportation mechanism is a molecular carrier mechanism, and living cell experiments show that a fluorescent peptide cargo can be delivered into the cytosol.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Engineering, Chemical
Miriam Mindova, Petr Distler, Jan John, Karel Stamberg, Dmytro Bavol, Suzan El Anwar, Bohumir Gruner
Summary: The behavior of the CHALMEX system with CyMe4-BTBP extractant in a mixture of 30% tri-n-butyl phosphate and 70% phenyl trifluoromethyl sulfone was studied. A kinetic model based on mass transfer was found to accurately describe the extraction of Am(III) and Eu(III). The distribution coefficients were determined based on temperature, allowing the calculation of changes in free enthalpy and entropy. After irradiation, it was found that radiolytic degradation products/adducts were efficient extractants for Am(III) and Eu(III), operating through an ion-exchange mechanism.
SEPARATION AND PURIFICATION TECHNOLOGY
(2023)
