Neutrophil extracellular traps in tumor metabolism and microenvironment

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 23, 2025

Neutrophil extracellular traps (NETs) are intricate, web-like formations composed of DNA, histones, and antimicrobial proteins, released by neutrophils. These structures participate in a wide array physiological pathological activities, including immune rheumatic diseases damage to target organs. Recently, the connection between NETs cancer has garnered significant attention. Within tumor microenvironment metabolism, exhibit multifaceted roles, such as promoting proliferation migration cells, influencing redox balance, triggering angiogenesis, driving metabolic reprogramming. This review offers comprehensive analysis link emphasizing areas that remain underexplored. include interaction with mitochondria, their effect on states within tumors, involvement reprogramming, contribution angiogenesis tumors. Such insights lay theoretical foundation for deeper understanding role development. Moreover, also delves into potential therapeutic strategies suggests future research directions, offering new perspectives treatment other related diseases.

Язык: Английский

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Cancer Development and Progression Through a Vicious Cycle of DNA Damage and Inflammation

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3352 - 3352

Опубликована: Апрель 3, 2025

Infections and chronic inflammation play a crucial role in the development of cancer. During inflammatory processes, reactive oxygen nitrogen species are generated by both epithelial cells, leading to induction oxidative nitrative DNA damage, such as formation 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) 8-nitroguanine (8-nitroG). These alterations can trigger mutations, which believed contribute cancer driven inflammation. The authors observed generation 8-nitroG through iNOS expression human animal tissues under conditions, where is likely develop. 8-NitroG serves predictive prognostic indicator for cancers linked Inflammation causes subsequent damage response create an environment marked hypoxia, with HMGB1 being key factor. interplay between HIF-1α, NF-ĸB, sustains accumulation driving progression worsening prognosis. involved not only onset advancement but also its conversion. Herein, propose vicious cycle (initiation promotion) progression, including conversion, via HMGB1.

Язык: Английский

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Metformin Inhibits Cell Motility and Proliferation of Triple-Negative Breast Cancer Cells by Blocking HMGB1/RAGE Signaling

Cells, Год журнала: 2025, Номер 14(8), С. 590 - 590

Опубликована: Апрель 13, 2025

High-mobility group box 1 (HMGB1) is a nuclear chromatin protein overexpressed in various cancers and linked to tumor progression. Outside the cell, HMGB1 binds receptors such as receptor for advanced glycation end products (RAGE), promoting metastasis. Targeting this signaling pathway may provide new therapeutic strategy aggressive cancers. Metformin, well-established antidiabetic drug, directly interacts with HMGB1, inhibiting its pro-inflammatory functions. This study investigates metformin’s effects on HMGB1/RAGE triple-negative breast cancer (TNBC) cells. Using wound-healing colony formation assays, we demonstrate that metformin reduces HMGB1-induced cell migration proliferation. Immunoblotting immunofluorescence analyses reveal decreases RAGE stabilization membrane, disrupts NF-κB signaling, reverses epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin, reducing vimentin, stabilizing β-catenin at membrane. Furthermore, lowers levels, disrupting positive feedback loop promotes aggressiveness. These findings highlight potential agent TNBC HMGB1/RAGE-driven

Язык: Английский

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Exploring the potential of Cucurbitacin analogs as HMGB1 inhibitors in glioblastoma multiforme: Insights from molecular docking and MD simulation of various triterpenoids

Journal of Molecular Liquids, Год журнала: 2025, Номер unknown, С. 127555 - 127555

Опубликована: Апрель 1, 2025

Язык: Английский

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Targeting HMGB1 and Its Interaction with Receptors: Challenges and Future Directions

Journal of Medicinal Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 9, 2024

High mobility group box 1 (HMGB1) is a nonhistone chromatin protein predominantly located in the nucleus. However, under pathological conditions, HMGB1 can translocate from nucleus to cytoplasm and subsequently be released into extracellular space through both active secretion passive release mechanisms. The distinct cellular locations of facilitate its interaction with various endogenous exogenous factors, allowing it perform diverse functions across range diseases. This Perspective provides comprehensive overview structure, mechanisms, multifaceted roles disease contexts. Furthermore, introduces development small molecule macromolecule inhibitors targeting receptors. A detailed analysis predicted pockets also presented, aiming establish foundation for future design inhibitors.

Язык: Английский

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γ‐Glutamylcysteine Ameliorates LPS‐Induced Inflammatory Responses in BV2 Cells via Activating Autophagy

Journal of Food Biochemistry, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

In neurodegenerative diseases, the activation of microglia and ensuing neuroinflammation are pivotal in regulating disease progression. Attenuating inflammation induced by microglial cells is considered a key strategy for slowing progression diseases. γ‐glutamylcysteine (γ‐GC) has exhibited significant antioxidative anti‐inflammatory effects; nevertheless, its potential role modulating neuroinflammatory responses remains incompletely explored. The current investigation aimed to establish model stimulating BV2 with lipopolysaccharide (LPS) explore protective effect γ‐GC on cells. results demonstrated that significantly attenuated LPS‐induced oxidative damage cells, reduced levels tumor necrosis factor‐α (TNF‐α) interleukin‐1β (IL‐1β), inhibited cytoplasmic translocation high‐mobility group box 1 protein (HMGB1), effectively mitigated inflammatory response We further investigated regulatory mechanism found enhances autophagy resulting marked reduction mammalian target rapamycin (mTOR) phosphorylation an increase AMP‐activated kinase (AMPK) levels. use inhibitors 3‐methyladenine (3‐MA) AMPK corroborates proposition promotes while suppressing through AMPK‐mTOR pathway. findings indicate exerts substantial inhibitory impact neuroinflammation, making it promising candidate development therapeutic strategies against disorders related conditions.

Язык: Английский

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NETs exacerbate placental inflammation and injury through high mobility group protein B1 during preeclampsia

Placenta, Год журнала: 2024, Номер 159, С. 131 - 139

Опубликована: Дек. 12, 2024

Inflammatory stress at the maternal-fetal interface plays an important role in occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) are believed to be among main pathogenic factors leading preeclampsia worsening its symptoms. However, underlying mechanism is largely unclear. This study aimed elucidate high mobility group box 1 (HMGB1) NETs involved pathogenesis PE. The concentration was detected plasma patients with PE using enzyme-linked immunosorbent assay (ELISA). Placental samples were collected from detect expression HMGB1 through Western Blot PCR. For vitro experiments, human trophoblast HTR-8/SVneo cells treated NETs, their proliferation, invasion, migration, apoptosis ability; degree oxidative stress; secretion inflammatory detected. Compared that normal pregnant women, increase release observed peripheral blood increased placenta colocalized NETs. treatment resulted inhibition cell invasion migration increases reactive oxygen species (ROS), several (IL-1β, IL-6, IL-8, TNF-α). These damaging effects can reversed scavenger glycyrrhizin, which indicates mediate damage HMGB1. cause inflammation-related functional during preeclampsia. produces a marked effect cascade involving Inhibiting suppress possible approach for future

Язык: Английский

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Diabetes Driven Oncogenesis and Anticancer Potential of Repurposed Antidiabetic Drug: A Systemic Review

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(3), С. 1907 - 1929

Опубликована: Июль 2, 2024

Язык: Английский

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