Review
Biochemistry & Molecular Biology
Adeleh Sahebnasagh, Fatemeh Saghafi, Sina Negintaji, Tingyan Hu, Mojtaba Shabani-Borujeni, Mohammadreza Safdari, Hassan Rezai Ghaleno, Lingchao Miao, Yaping Qi, Mingfu Wang, Pan Liao, Antoni Sureda, Jesus Simal-Gandara, Seyed Mohammad Nabavi, Jianbo Xiao
Summary: This review focuses on the immunomodulatory role of nitric oxide (NO) in cancer and recent advancements in the use of NO donors in immunotherapy. It is suggested that low/moderate levels of NO may promote tumorigenesis, while higher levels have anti-tumor effects. The use of NO donors in immunotherapy shows therapeutic potential, although clinical trials are lacking.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Mariana Brandi Mendonca Pinheiro, Stephane Vicente Rozini, Anna Cecillia Quirino-Teixeira, Giselle Barbosa-Lima, Juliana F. Lopes, Carolina Q. Sacramento, Fernando A. Bozza, Patricia T. Bozza, Eugenio D. Hottz
Summary: This study found that platelets from dengue patients express iNOS and produce higher levels of NO, which is associated with warning signs, hypoalbuminemia, and hemorrhagic manifestations. The researchers discovered that circulating inflammatory mediators, specifically IL-1 beta, can induce iNOS expression and NO synthesis in platelets. Additionally, platelet infection with DENV led to iNOS expression and NO production, and treatment with IL-1 receptor antagonist or anti-IL-1 antibodies prevented this.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Chemistry, Medicinal
Achini K. Vidanapathirana, Peter J. Psaltis, Christina A. Bursill, Andrew D. Abell, Stephen J. Nicholls
Summary: Nitric oxide (NO) is a vital cellular signaling molecule in maintaining cardiovascular function by regulating vascular tone and blood flow. Accurate, real-time bioimaging of NO is crucial for clinical applications within the cardiovascular system, but faces challenges due to the wide physiological range of NO and limitations of current imaging methods. Development of biocompatible nanoscale sensors holds promise for bioimaging NO in cardiovascular pathologies.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Medicine, Research & Experimental
George J. Dugbartey
Summary: Kidney transplantation is the preferred treatment for patients with kidney failure. However, ischemia-reperfusion injury (IRI) poses a significant challenge to the long-term success of this intervention. Nitric oxide (NO) has emerged as a potential candidate for mitigating IRI and preventing graft rejection in kidney transplantation. This review provides an overview of the sources and protective effects of endogenous and exogenous NO in kidney transplantation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Plant Sciences
Zhi-Hu Lin, Jinsong Hu, Huagang Shi, Chia-Ching Liaw, Wei-Lun Qiu, Wei-Hung Hsu, Tung-Yi Lin
Summary: The study demonstrated that water extract of medical ink (WEMI) had no cytotoxic effect on murine macrophage Raw264.7 cells and slightly rescued LPS-suppressed cell viability. WEMI did not induce NO production or IL-6 secretion, but significantly induced secretion of TNF-alpha. Additionally, WEMI effectively reduced LPS-induced NO production.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Mona F. Mahmoud, Asmaa M. Elmaghraby, Noura Ali, Islam Mostafa, Assem M. El-Shazly, Mohamed A. O. Abdelfattah, Mansour Sobeh
Summary: Black pepper oil mitigates glycemic parameters, dyslipidemia, oxidative and nitrosative stress, and pancreatic fibrosis in dexamethasone-treated rats.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Huashan Liu, Zhenxing Liang, Sijing Cheng, Liang Huang, Wenxin Li, Chi Zhou, Xiaobin Zheng, Shujuan Li, Ziwei Zeng, Liang Kang
Summary: The study reveals that mutant KRAS plays a crucial role in tumor immune evasion in colorectal cancer. Reduced infiltration of cytotoxic CD8(+) T cells is observed in colorectal cancer specimens with mutant KRAS compared to wild type KRAS. Preclinical models confirm this finding and show poor response to anti-PD-1 and adoptive T-cell therapies in KRAS mutant tumors. Mechanistic analysis reveals that lactic acid derived from mutant KRAS-expressing tumor cells sensitizes tumor-specific cytotoxic CD8(+) T cells to activation-induced cell death through NF-kappa B inactivation, explaining the inverse association between intratumoral cytotoxic CD8(+) T cells and KRAS mutation. Importantly, KRAS mutated tumor resistance to immunotherapies can be overcome by targeting KRAS or inhibiting lactic acid production. This study suggests the potential of targeting the KRAS-mediated immune program for the treatment of patients with KRAS mutant colorectal cancer.
Article
Biochemistry & Molecular Biology
Di Li, Jinlin He, Caihong Fang, Yiwen Zhang, Mingli He, Zhanqi Zhang, Jinsong Hou, Qiong Xu
Summary: Excessive differentiation of osteoclasts contributes to the disruption of bone homeostasis in inflammatory bone diseases. METTL3 deficiency leads to decreased osteoclast differentiation and increased apoptosis in inflammatory conditions, possibly due to the exacerbation of iNOS/NO-mediated mitochondrial dysfunction by promoting Nos2 mRNA stability in a YTHDF1-dependent manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Yading Zhao, Dandan Shi, Lu Guo, Mengmeng Shang, Xiao Sun, Dong Meng, Shan Xiao, Xiaoxuan Wang, Jie Li
Summary: This study developed a novel acidity-responsive nanoscale ultrasound contrast agent, L-Arg@PTX nanodroplets, for co-delivery of paclitaxel and L-arginine. These nanodroplets exhibited uniform size and high drug loading efficiency, enabling good ultrasound diagnostic imaging capability and improved tumor aggregation. Combined with ultrasound targeted microbubble destruction (UTMD), the nanodroplets increased cellular reactive oxygen species, alleviating hypoxia and increasing cytotoxic T lymphocytes infiltration, and synergistically enhancing immunotherapy with PTX-induced immunogenic cell death.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Katie Lin, Stavroula Baritaki, Silvia Vivarelli, Luca Falzone, Aurora Scalisi, Massimo Libra, Benjamin Bonavida
Summary: This article reviews the molecular regulation of protooncogene and iNOS expression in breast cancer, explores the interrelationships between iNOS, HER2, BRCA1/2, and NO metabolism in the pathophysiology of cancer stem cells, and proposes further research into the regulatory mechanisms underlying iNOS and various breast cancer oncogenes.
Article
Biochemistry & Molecular Biology
Jaqueline Pereira Moura Soares, Diego Assis Goncalves, Ricardo Xisto de Sousa, Margareth Gori Mouro, Elisa M. S. Higa, Leticia Paulino Sperandio, Carolina Moraes Vitoriano, Elisa Bachir Santa Rosa, Fernanda Oliveira dos Santos, Gustavo Nery de Queiroz, Roberta Sessa Stilhano Yamaguchi, Gustavo Pereira, Marcelo Yudi Icimoto, Fabiana Henriques Machado de Melo
Summary: Cutaneous melanoma is the most aggressive type of skin cancer, and it progresses through different stages. Reactive oxygen species modulate oncogenic signaling pathways in all stages of melanoma development. The altered concentration of tetrahydrobiopterin disrupts cellular redox homeostasis and contributes to melanoma progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Robert J. Webber, Richard M. Sweet, Douglas S. Webber
Summary: The study found that anti-MV-A iNOS monoclonal antibodies can mitigate the harmful effects of MV-A iNOS and increase the survival rate of mice challenged with sepsis. The efficacy of the treatment is both time- and dose-dependent. Humanized anti-MV-A iNOS mAbs could potentially save tens of thousands of lives annually and improve antibiotic stewardship.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Himadri Shekhar Roy, Rupali Singh, Deepa Ghosh
Summary: Nitric oxide (NO) plays a critical role in the development of osteoarthritis (OA), and inhibiting its release through iNOS inhibition is an attractive therapeutic target. However, existing molecules have limitations, leading to a lack of successful clinical applications. The development of nanotechnology has revived interest in targeting NO to prevent cartilage degeneration.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2021)
Article
Neurosciences
Yoshihiko Nakatani, Manami Yaguchi, Kazuki Ogino, Risako Noguchi, Naoki Yamamoto, Taku Amano
Summary: Duloxetine can effectively reduce the production of NO induced by LPS and inhibit the protein expression levels of iNOS, phosphorylated-I kappa B alpha, phosphorylated-Akt, and Akt induced by LPS. However, it does not have an effect on other pro-inflammatory factors or the phosphorylation ratios of certain molecules.
PSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haider H. Dar, Tamil S. Anthonymuthu, Liubov A. Ponomareva, Austin B. Souryavong, Galina V. Shurin, Alexandr O. Kapralov, Vladimir A. Tyurin, Janet S. Lee, Rama K. Mallampalli, Sally E. Wenzel, Huelya Bayir, Valerian E. Kagan
Summary: The research found that Pseudomonas aeruginosa degrades host GPx4 defense through activating lysosomal chaperone-mediated autophagy, leading to the activation of the host's anti-ferroptotic mechanism driven by iNOS/NO'. Macrophage-produced NO' can distantly prevent P. aeruginosa-induced ferroptosis in epithelial cells by suppressing phospholipid peroxidation.
Article
Oncology
Sisca Ucche, Satoru Yokoyama, Marija Mojic, Kohei Oki, Chikako Ohshima, Haruka Tsuihiji, Ichiro Takasaki, Hideaki Tahara, Yoshihiro Hayakawa
Summary: This study investigates how tumor cells escape from the immune response by analyzing immune-escape variants of melanoma cells. The researchers identify GSTA4 as a critical molecule in this process and find that immune escape melanoma variants acquire greater metastatic ability through a GSTA4-dependent mechanism.
MOLECULAR CANCER RESEARCH
(2023)
Article
Chemistry, Medicinal
Liridona Useini, Marija Mojic, Markus Laube, Peter Loennecke, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Jens Pietzsch, Evamarie Hey-Hawkins
Summary: Fenoprofen is a common NSAID used to treat rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis, and gout. It inhibits the synthesis of prostaglandins by blocking both COX-1 and COX-2 isoforms. Modifications using carborane clusters showed stronger antitumor potential compared to aryl-based compounds.
Article
Immunology
Qing Li, Jialuo He, Senlin Li, Cheng Tian, Jian Yang, Huimin Yuan, Yi Lu, Paolo Fagone, Ferdinando Nicoletti, Ming Xiang
Summary: Pancreatic cancer (PC) has a cold tumor immune microenvironment (TIME) with minimal dendritic cell (DC) and T cell infiltration, leading to inadequate immunotherapy and chemotherapy. Combining gemcitabine (GEM) with ginsenoside Rh2 (Rh2) can enhance tumor immunogenicity and induce lasting anti-tumor immunity in PC. The activation of DCs by Rh2 via the CARD9-BCL10-MALT1/NF-KB pathway may reverse the cold TIME and optimize GEM chemotherapy, providing a potentially feasible and safe treatment strategy for PC.
CLINICAL IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Milica Markelic, Marija Mojic, Dijana Bovan, Sanja Jelaca, Zorana Jovic, Milica Puric, Djuro Koruga, Sanja Mijatovic, Danijela Maksimovic-Ivanic
Summary: Our study demonstrated that treatment of melanoma cells with hyperpolarized light (HPL) and hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced cell viability and induced senescence and reprogramming towards normal phenotype. We investigated whether these effects persisted in vivo in a mouse melanoma model with combined treatment of HPL irradiation and 3HFWC. The results showed potent antitumor effects, including growth arrest, senescent phenotype, melanocytic differentiation, and activation of antitumor immune response.
Article
Pharmacology & Pharmacy
Sebastian Braun, Svetlana Paskas, Markus Laube, Sven George, Bettina Hofmann, Peter Loennecke, Dieter Steinhilber, Jens Pietzsch, Sanja S. Mijatovic, Danijela Maksimovic-Ivanic, Evamarie Hey-Hawkins
Summary: In this study, carborane-containing dual COX-2/5-LO inhibitors were designed by incorporating metabolically stable, sterically demanding, and hydrophobic carboranes into existing inhibitors. Five carborane-containing derivatives showed high inhibitory activities towards COX-2 and 5-LO, with meta-carborane derivative 3 demonstrating higher anticancer activity compared to RWJ-63556. The accumulation of lipid droplets in cells indicated the blockage of COX-2 and 5-LO pathways, suggesting a promising approach for the design of potent dual COX-2/5-LO inhibitors.
ADVANCED THERAPEUTICS
(2023)
Article
Cardiac & Cardiovascular Systems
Carla Letizia Busceti, Albino Carrizzo, Franca Bianchi, Massimiliano De Lucia, Antonio Damato, Chiara Cazzin, Eleonora Venturini, Paola Di Pietro, Roxana Paula Ginerete, Luisa Di Menna, Maria Cotugno, Rosita Stanzione, Simona Marchitti, Serena Migliarino, Michele Ciccarelli, Sebastiano Sciarretta, Valeria Bruno, Giuseppe Battaglia, Francesco Fornai, Massimo Volpe, Speranza Rubattu, Ferdinando Nicoletti, Carmine Vecchione
Summary: Dkk3 plays a crucial role in cardiovascular homeostasis, and its deficiency leads to hypertension and impaired vascular function, which can be rescued by restoring Dkk3 expression. This effect is achieved through promoting VEGF expression and activating the VEGF/Akt/eNOS hypotensive pathway.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Andrea Ferrigno, Marta Cagna, Oriana Bosco, Michelangelo Trucchi, Clarissa Berardo, Ferdinando Nicoletti, Mariapia Vairetti, Laura G. Di Pasqua
Summary: In this study, the effects of mGluR5 blockade were evaluated in a mouse model of steatosis. It was found that MPEP can reduce fat accumulation and oxidative stress. This study provides the first in vivo evidence of the beneficial effects of MPEP in a murine model of steatosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ralitza Alexova, Simona Alexandrova, Stela Dragomanova, Reni Kalfin, Ayten Solak, Sidharth Mehan, Maria Cristina Petralia, Paolo Fagone, Katia Mangano, Ferdinando Nicoletti, Lyubka Tancheva
Summary: Pomegranate is a rich source of polyphenols that have anti-inflammatory and antioxidant activity, and can support the immune system during viral infection and recovery. Studies have shown that pomegranate polyphenol extract and its components can control immune cell infiltration, regulate cytokine secretion, inhibit viruses like SARS-CoV-2, and modulate the NF-κB pathway. Further research is needed to understand the interactions between polyphenols, viruses, and the host immune response.
Article
Pharmacology & Pharmacy
Liridona Useini, Teodora Komazec, Markus Laube, Peter Loennecke, Jonas Schaedlich, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Jens Pietzsch, Evamarie Hey-Hawkins
Summary: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain, fever, and inflammation, and have reported antitumor properties. Selectivity for the COX-2 isoform of NSAIDs is of high interest to reduce off-target effects. Modified NSAIDs using carborane clusters show altered selectivity profile and isonimesulide and its carborane derivatives exhibit stronger antitumor potential compared to nimesulide and isonimesulide. Additionally, replacement of the phenyl ring with a carborane moiety shifts the COX activity from nonactive to active compounds.
ADVANCED THERAPEUTICS
(2023)
Article
Immunology
Katia Mangano, Maria Cristina Petralia, Rita Bella, Manuela Pennisi, Jose Francisco Munoz-Valle, Jorge Hernandez-Bello, Ferdinando Nicoletti, Paolo Fagone
Summary: This study evaluated the expression levels of galectin-3 in different cell populations involved in the pathogenesis of multiple sclerosis (MS). Higher levels of galectin-3 were observed in encephalitogenic CD4+ T cells, microglial cells, astrocytes, and oligodendrocytes from MS models and human MS-related white matter lesions. Galectin-3 was found to be co-expressed with genes involved in the regulation of microglia, cytokine production, and chemotaxis. This study provides comprehensive evidence for the potential pathogenic role of galectin-3 in the development of MS.
IMMUNOLOGIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ivana Nikolic, Jelena Samardzic, Strahinja Stevanovic, Jovanka Miljus-Dukic, Mira Milisavljevic, Gordana Timotijevic
Summary: Global climate change has negative effects on plant growth and agriculture. Understanding the molecular mechanisms and developing plants tolerant to abiotic stress are crucial. This study uses CRISPR/Cas9 technology to investigate the role of DSS1 protein in plant response to oxidative stress. Two highly homologous DSS1 genes in Arabidopsis, AtDSS1(I) and AtDSS1(V), were mutated and analyzed for their sensitivity to oxidative stress. Results showed differences in root and stem lengths, as well as survival rates and protein oxidation levels in mutant plants compared to wild-type plants. The study suggests that DSS1(V) protein may play an important role in plant abiotic stress response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Philipp Stockmann, Lydia Kuhnert, Tamara Krajnovic, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Walther Honscha, Evamarie Hey-Hawkins
Summary: The study introduces a new compound DMQCd, which shows promising results in improving multidrug resistance in cancer treatment by inhibiting the human ABCG2 transporter. The results indicate that DMQCd exhibits superior cytotoxicity and ability to reverse resistance.
Article
Chemistry, Medicinal
Svetlana Paskas, Philipp Stockmann, Sanja Mijatovic, Lydia Kuhnert, Walther Honscha, Evamarie Hey-Hawkins, Danijela Maksimovic-Ivanic
Summary: The ABCG2 transporter protein plays an important role in multidrug resistance and targeting its activity can improve cancer therapies. This study evaluates potential inhibitors of ABCG2 and their toxicity towards cancer cells expressing ABCG2. The results show that some inhibitors can increase the efficacy of therapeutic agents through synergistic effects, and suggest the possible targeting of both ABCG2 and ABCB1 transporters.
Article
Biochemistry & Molecular Biology
Aleksandr Kazimir, Benedikt Schwarze, Peter Loennecke, Sanja Jelaca, Sanja Mijatovic, Danijela Maksimovic-Ivanic, Evamarie Hey-Hawkins
Summary: This study evaluates the potential of a copper-tamoxifen hybrid complex as a therapeutic candidate for breast cancer. The results show that the complex exhibits remarkable activity against different types of breast cancer cell lines, highlighting its efficacy through diverse mechanisms of action.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Moon Hee Lee, Jason Theodoropoulos, Jani Huuhtanen, Dipabarna Bhattacharya, Petrus Jarvinen, Sara Tornberg, Harry Nisen, Tuomas Mirtti, Ilona Uski, Anita Kumari, Karita Peltonen, Arianna Draghi, Marco Donia, Anna Kreutzman, Satu Mustjoki
Summary: In this study, we investigated the expanded tumor-infiltrating lymphocytes (TILs) in patients with renal cell carcinoma (RCC) and explored their characteristics and ability to recognize the tumor using experimental and computational tools.
CANCER RESEARCH COMMUNICATIONS
(2023)
