Essential metals in health and disease

Chemico-Biological Interactions, Journal Year: 2022, Volume and Issue: 367, P. 110173 - 110173

Published: Sept. 22, 2022

In total, twenty elements appear to be essential for the correct functioning of human body, half which are metals and non-metals. Among those that currently considered normal biological four main group elements, sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), six d-block transition metal manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn) molybdenum (Mo). Cells have developed various metallo-regulatory mechanisms maintaining a necessary homeostasis metal-ions diverse cellular processes, most importantly in central nervous system. Since redox active (for example Fe Cu) may participate electron transfer reactions, their must carefully controlled. The catalytic behaviour escaped control, e.g. via Fenton reaction, results formation reactive hydroxyl radicals, cause damage DNA, proteins membranes. Transition integral parts centers numerous enzymes (e.g. Cu,Zn-SOD, Mn-SOD, Catalase) catalyze chemical reactions at physiologically compatible rates. Either deficiency, or an excess result disease states arising organism. Some typical ailments characterized by disturbed include neurological disorders (Alzheimer's, Parkinson's Huntington's disorders), mental health problems, cardiovascular diseases, cancer, diabetes. To comprehend more deeply metals, acting either alone combination, and/or through interaction with non-essential chromium) function systems will require application broader, interdisciplinary approach than has mainly been used so far. It is clear stronger cooperation between bioinorganic chemists biophysicists - who already achieved great success understanding structure role metalloenzymes living biologists, access new avenues research biology ions. With this mind, present paper reviews selected aspects ions possible interactions under pathological conditions.

Language: Английский

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Advancing glioblastoma treatment by targeting metabolism

Neoplasia, Journal Year: 2024, Volume and Issue: 51, P. 100985 - 100985

Published: March 12, 2024

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand tumor cells, including proliferation, growth, and survival. Many genes, proteins, metabolites associated with GBM have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, becoming increasingly explore role internal external factors metabolic regulation order identify more precise therapeutic diagnostic markers GBM. In this review, we define characteristics GBM, investigate specificities such targetable vulnerabilities resistance, well present current efforts target improve standard care.

Language: Английский

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Glioblastoma multiforme: insights into pathogenesis, key signaling pathways, and therapeutic strategies

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 26, 2025

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor in adults, characterized by a poor prognosis significant resistance to existing treatments. Despite progress therapeutic strategies, median overall survival remains approximately 15 months. A hallmark of GBM its intricate molecular profile, driven disruptions multiple signaling pathways, including PI3K/AKT/mTOR, Wnt, NF-κB, TGF-β, critical growth, invasion, treatment resistance. This review examines epidemiology, mechanisms, prospects targeting these pathways GBM, highlighting recent insights into pathway interactions discovering new targets improve patient outcomes.

Language: Английский

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Metabolic Reprogramming of Tumor-Associated Macrophages Using Glutamine Antagonist JHU083 Drives Tumor Immunity in Myeloid-Rich Prostate and Bladder Cancers

Cancer Immunology Research, Journal Year: 2024, Volume and Issue: 12(7), P. 854 - 875

Published: April 26, 2024

Abstract Glutamine metabolism in tumor microenvironments critically regulates antitumor immunity. Using the glutamine-antagonist prodrug JHU083, we report potent growth inhibition urologic tumors by JHU083-reprogrammed tumor-associated macrophages (TAMs) and tumor-infiltrating monocytes. We show JHU083-mediated glutamine antagonism induced TNF, proinflammatory, mTORC1 signaling intratumoral TAM clusters. TAMs also exhibited increased cell phagocytosis diminished proangiogenic capacities. In vivo of consumption resulted glycolysis, a broken tricarboxylic acid (TCA) cycle, purine disruption. Although effect on T cells was moderate, JHU083 promoted stem cell–like phenotype CD8+ decreased abundance regulatory cells. Finally, caused global shutdown glutamine-utilizing metabolic pathways cells, leading to reduced HIF-1α, c-MYC phosphorylation, induction apoptosis, all key features. Altogether, our findings demonstrate that targeting with led suppressed as well reprogramming immunosuppressive within prostate bladder immune responses. can offer an effective therapeutic benefit for types are enriched TAMs.

Language: Английский

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Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells

Metabolites, Journal Year: 2024, Volume and Issue: 14(5), P. 249 - 249

Published: April 25, 2024

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations the hypoxic tumor microenvironment, as well transcriptional and signaling networks, which result changes global genetic expression. pathways PI3K/AKT/mTOR RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, modulating factors p53, HIF1, c-Myc. overexpression of HIF1 c-Myc, master regulators cellular a key contributor to synthesis bioenergetic molecules mediate glioma transformation, proliferation, survival, migration, invasion modifying transcription levels gene groups involved metabolism. Meanwhile, tumor-suppressing protein negatively regulates often lost glioblastoma. Alterations this triad induce shift cells allows them adapt survive such mutations, hypoxia, acidosis, presence reactive oxygen species, nutrient deprivation, activity expression molecules, enzymes, metabolites, transporters, glycolysis glutamine pentose phosphate cycle, tricarboxylic acid oxidative phosphorylation, degradation fatty acids nucleic acids. This review summarizes our current knowledge on role p53 genic regulatory network for metabolism cells, potential therapeutic inhibitors these factors.

Language: Английский

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Mendelian randomization analysis of plasma proteins reveals potential novel tumor markers for gastric cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 28, 2025

This study aimed to elucidate the potential causal relationship between 4,907 plasma proteins and risk of gastric cancer using a two-sample Mendelian randomization approach. We utilized genome-wide association (GWAS) data perform analyses, treating as exposure factors outcome. Instrumental variables for were selected based on strongly correlated SNPs identified through processing screening GWAS provided by deCode database. employed set statistical methods centered inverse variance weighting (IVW) analysis estimate odds ratios (ORs) effects these susceptibility. According IVW method, 14 associated with (p < 0.005). Specifically, CHST15 (OR = 0.7553, 95% CI 0.6346 − 0.8988), L1CAM 0.7230, 0.5876 0.8896), FTMT 0.8246, 0.7241 0.9391), PMM2 0.5767, 0.3943 0.8433) negatively GASTRIC CANCER, whereas ABO 1.1868, 1.0638 1.3240), FAM3D 1.2109, 1.0850 1.3515), FAM3B 1.2988, 1.0953 1.5402), ADH7 1.3568, 1.1044 1.6670), MAP1LC3A 1.3704, 1.1194 1.6778), PGLYRP1 1.4071, 1.1235 1.7623), PDE5A 1.7446, 1.2693 2.3978), GLUL 3.1203, 1.5017 6.4839), NFE2L1 3.1759, 1.6163 6.2402), MAFG 3.1945, 1.5329 6.6575) positively correlated. Convergent results from Weighted Median MR-Egger analyses confirmed associations. Reverse indicated that does not significantly alter levels > 0.05). Sensitivity including assessments heterogeneity horizontal pleiotropy, robustness reliability our findings without significant bias. Pathway enrichment gene expression proteins, GO KEGG pathways, revealed CHST15, L1CAM, FTMT, may serve protective against cancer, while ABO, FAM3D, FAM3B, ADH7, MAP1LC3A, PGLYRP1, PDE5A, GLUL, NFE2L1, contribute pathogenesis. These highlight complex biological interactions tumorigenesis, providing valuable insights preventive therapeutic strategies in malignancy management.

Language: Английский

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Pancreatic stellate cells exploit Wnt/β-catenin/TCF7-mediated glutamine metabolism to promote pancreatic cancer cells growth

Cancer Letters, Journal Year: 2022, Volume and Issue: 555, P. 216040 - 216040

Published: Dec. 22, 2022

Language: Английский

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Glutamine Metabolism in Cancer Stem Cells: A Complex Liaison in the Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2337 - 2337

Published: Jan. 25, 2023

In this review we focus on the role of glutamine in control cancer stem cell (CSC) fate. We first provide an overview metabolism, and then summarize relevant studies investigating how metabolism modulates CSC compartment, concentrating solid tumors. schematically describe contributes to several metabolic pathways, such as redox ATP production, non-essential aminoacids nucleotides biosynthesis, ammonia production. Furthermore, show that is a key regulator epigenetic modifications CSC. Finally, briefly discuss cancer-associated fibroblasts, adipocytes, senescent cells tumor microenvironment may indirectly influence fate by modulating availability. aim highlight complexity glutamine's CSC, which supports our knowledge about heterogeneity within population.

Language: Английский

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Ovarian Cancer and Glutamine Metabolism

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 5041 - 5041

Published: March 6, 2023

Cancer cells are known to have a distinct metabolic profile and exhibit significant changes in variety of mechanisms compared normal cells, particularly glycolysis glutaminolysis, order cover their increased energy requirements. There is mounting evidence that there link between glutamine metabolism the proliferation cancer demonstrating vital mechanism for all cellular processes, including development cancer. Detailed knowledge regarding its degree engagement numerous biological processes across types still lacking, despite fact such necessary comprehending differentiating characteristics many forms This review aims examine data on ovarian identify possible therapeutic targets treatment.

Language: Английский

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L-asparaginase anti-tumor activity in pancreatic cancer is dependent on its glutaminase activity and resistance is mediated by glutamine synthetase

Experimental Cell Research, Journal Year: 2023, Volume and Issue: 426(2), P. 113568 - 113568

Published: March 24, 2023

Language: Английский

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