The unbroken Krebs cycle. Hormonal‐like regulation and mitochondrial signaling to control mitophagy and prevent cell death DOI Creative Commons
Rafael Franco, Joan Serrano‐Marín

BioEssays, Journal Year: 2022, Volume and Issue: 45(3)

Published: Dec. 22, 2022

The tricarboxylic acid (TCA) or Krebs cycle, which takes place in prokaryotic cells and the mitochondria of eukaryotic cells, is central to life on Earth participates key events such as energy production anabolic processes. Despite its relevance, it not perceived tightly regulated compared other metabolisms glycolysis/gluconeogenesis. A better understanding functioning TCA cycle crucial due mitochondrial function impairment several diseases, especially those that occur with neurodegeneration. This article revisits what known about regulation hypothesizes need for large-scale, rapid enzyme activity. Evidence activity by activation/deactivation protein kinases phosphatases exists literature. Apart from indirect via G protein-coupled receptors (GPCRs) at cell surface, signaling upon activation GPCRs membranes may lead a direct enzymes cycle. Hormonal-like posttranscriptional mediated activable deserve proper assessment using isolated mitochondria. Also see video abstract here: https://youtu.be/aBpDSWiMQyI.

Language: Английский

A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle DOI Creative Commons
Bolin Wang,

Jinli Pei,

Shengnan Xu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: March 8, 2024

Abstract Glutamine metabolism plays a pivotal role in cancer progression, immune cell function, and the modulation of tumor microenvironment. Dysregulated glutamine has been implicated development responses, supported by mounting evidence. Cancer cells heavily rely on as critical nutrient for survival proliferation, while require activation proliferation during reactions. This metabolic competition creates dynamic tug-of-war between cells. Targeting transporters downstream enzymes involved holds significant promise enhancing anti-tumor immunity. A comprehensive understanding intricate molecular mechanisms underlying this interplay is crucial developing innovative therapeutic approaches that improve immunity patient outcomes. In review, we provide overview recent advances unraveling explore potential applications basic science discoveries clinical setting. Further investigations into regulation are expected to yield valuable insights, paving way future interventions.

Language: Английский

Citations

24
Matrix Metalloproteinases (MMPs) as Novel Prognostic Biomarkers to Predict Disease Progression, Survival Duration, and Recurrence Rate in Oral Cancer Patients DOI Creative Commons
Jyoti Saini, Jaimanti Bakshi, Naresh K. Panda

et al.

Indian Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

Citations

2
Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets DOI Creative Commons
Ding Nan,

Weiping Yao,

Luanluan Huang

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 24, 2025

Language: Английский

Citations

2
Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets DOI Creative Commons

Ashley Irin Cortes Ballen,

Maryam Amosu,

Surya Ravinder

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1574 - 1574

Published: Sept. 19, 2024

Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth a poor prognosis for patients. Despite advancements in treatment, the median survival time GBM patients remains low. One of crucial challenges understanding treating GBMs involves its remarkable cellular heterogeneity adaptability. Central to proliferation cells their ability undergo metabolic reprogramming. Metabolic reprogramming process that allows cancer alter metabolism meet increased demands survive often oxygen- nutrient-deficient microenvironment. These changes include Warburg effect, alterations several key pathways including glutamine metabolism, fatty acid synthesis, tricarboxylic (TCA) cycle, uptake utilization glutamine, more. complexity adaptability deeper offers hope developing more effective therapeutic interventions against GBMs.

Language: Английский

Citations

6
Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems DOI Open Access
Aisha Farhana, Abdullah Alsrhani, Yusuf S. Khan

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3836 - 3836

Published: July 28, 2023

Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory conventional diagnostic chemotherapeutics due their limited targetability, specificity, solubility, side effects. The inherent ability of each cancer evolve through various genetic epigenetic transformations metabolic reprogramming underlies limitations. Though tumor microenvironments (TMEs) quite well understood some cancers, microenvironment differs from other internal perturbations skew thereby impeding development appropriate diagnostics, drugs, vaccines, therapies. associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation resistant niches progression, a thorough understanding crucial However, this remains missing element theranostics, necessitating modalities that can be adapted for diagnostics therapeutics. In challenging scenario, nanomaterials modular platforms TME achieving successful theranostics. Several nanoscale particles have been successfully researched animal models, few reached clinical trials, achieved Nanoparticles exhibit intrinsic capability interact with diverse biomolecules modulate functions. Furthermore, nanoparticles functionalized receptors, modulators, drugs facilitate specific targeting reduced toxicity. This review discusses current different theranostic nanosystems, synthesis, functionalization, targetability modulation bioenergetics, microenvironment. We highlight potential nanosystems enhanced chemotherapeutic success emphasizing questions remain unanswered.

Language: Английский

Citations

13
Metabolic Fingerprint in Childhood Acute Lymphoblastic Leukemia DOI Creative Commons
Maria Papadopoulou, Paraskevi Panagopoulou,

Efstathia I. Paramera

et al.

Diagnostics, Journal Year: 2024, Volume and Issue: 14(7), P. 682 - 682

Published: March 24, 2024

Introduction: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy. Despite high cure rates, several questions remain regarding predisposition, response to treatment, and prognosis of disease. The role intermediary metabolism in individualized mechanistic pathways disease unclear. We have hypothesized that children with any (sub)type ALL a distinct metabolomic fingerprint at diagnosis when compared: (i) control group; (ii) different ALL; (iii) end induction treatment. Materials Methods: In this prospective case–control study (NCT03035344), plasma urinary metabolites were analyzed 34 before beginning (D0) treatment (D33). Their metabolic was defined by targeted analysis 106 compared an equal number matched controls. Multivariate univariate statistical analyses performed using SIMCAP scripts under R programming language. Results: Metabolomic showed changes patients controls on both D0 D33. within patient group differed significantly between common B-ALL pre-B D33, reflecting effect further identified major components dysregulation, indicating shifts fatty acid synthesis, transfer oxidation, amino glycerophospholipid metabolism, glutaminolysis/TCA cycle. Conclusions: type time point-specific alterations observed pediatric are particular interest as they may offer potential for discovery new prognostic biomarkers therapeutic targets.

Language: Английский

Citations

5
Glutamine attenuates bisphenol A-induced intestinal inflammation by regulating gut microbiota and TLR4-p38/MAPK-NF-κB pathway in piglets DOI Creative Commons
Zi-Hao Liu, Min Liu, Huiru Wang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 270, P. 115836 - 115836

Published: Dec. 27, 2023

Bisphenol A (BPA), as a kind of widely exerted environmental hazardous material, brings toxicity to both humans and animals. This study aimed investigate the role glutamine (Gln) in intestinal inflammation microbiota BPA-challenged piglets. Thirty-two piglets were randomly divided into four groups according 2 factors including BPA (0 vs. 0.1%) Gln 1%) supplemented basal diet for 42-day feeding experiment. The results showed exposure impaired piglet growth, induced disturbed balance. However, dietary supplementation improved growth performance, while decreasing serum pro-inflammatory cytokine levels In addition, attenuated mucosal damage by normalizing activation toll-like receptor 4 (TLR4)-p38/MAPK-nuclear factor-kappa B (NF-κB) pathway caused BPA. Moreover, decreased abundance Actinobacteriota Proteobacteria, Roseburia, Prevotella, Romboutsia Phascolarctobacterium content short-chain fatty acids cecum contents exposure. there potential relevance between gut cytokines cecal acids. conclusion, is critical nutrition attenuating BPA-induced inflammation, which partially mediated regulating microbial balance suppressing TLR4/p38 MAPK/NF-κB signaling.

Language: Английский

Citations

13
Warburg Effect Revisited: Embodiment of Classical Biochemistry and Organic Chemistry. Current State and Prospects DOI
Leonid G. Menchikov, Alexander A. Shestov, Anatoliy V. Popov

et al.

Biochemistry (Moscow), Journal Year: 2023, Volume and Issue: 88(S1), P. S1 - S20

Published: Jan. 1, 2023

Language: Английский

Citations

11
Evaluation of Anticancer Activity of Novel and Tumor-Targeted Glutamine-Conjugated Organotin(IV) Compounds in Colorectal Cancer─An In Vitro and In Vivo Study DOI
Shagun Sharma, Varinder Kaur,

Pratibha Duhan

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Over the years, numerous ligand-based organotin(IV) Schiff base compounds have shown remarkable cytotoxicity and anticancer activities, but their clinical use is restricted by systemic toxicity, prompting search for targeted therapies. Targeted delivery can be enhanced exploiting inherent characteristics of cancer cells such as glutamine addiction, which essential to support cellular biosynthesis cell growth sustain aberrant proliferation. Our previous study revealed glutamine-conjugated strong DNA/protein affinities, favorable in silico ADME profiles, significant antiproliferative activity. In this study, these demonstrated against human colon carcinoma adenocarcinoma lines via induction cycle arrest apoptosis. DMH/DSS-induced experimental carcinogenesis, reduced tumor burden volume inhibited proliferation induced apoptosis, with minimal toxicity. Tissue distribution studies selective accumulation colon. These findings potential chemotherapeutic candidates cancer.

Language: Английский

Citations

0
Oleic acid stimulates proliferation of RMG-1 ovarian cancer cells by activating the pentose phosphate pathway and glutamine metabolism DOI

Takeru Tamaki,

Nobuyuki Fukushima

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 722, P. 150162 - 150162

Published: May 24, 2024

Language: Английский

Citations

3