Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Mitochondrion, Journal Year: 2024, Volume and Issue: 78, P. 101942 - 101942
Published: Aug. 6, 2024
Language: Английский
Citations
11
Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924
Published: Nov. 20, 2024
Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.
Language: Английский
Citations
8
BMC Pharmacology and Toxicology, Journal Year: 2025, Volume and Issue: 26(1)
Published: Jan. 22, 2025
Diabetic neuropathy (DN) is a heterogeneous condition characterized by complex pathophysiological changes affecting both autonomic and somatic components of the nervous system. Inflammation oxidative stress are recognized contributors to pathogenesis DN. This study aims evaluate therapeutic potential dichloroacetic acid (DCA) in alleviating DN symptoms, focusing on its anti-inflammatory antioxidant properties. Thirty-two adult male Sprague Dawley rats were divided into four groups: Control, Diabetic, two DCA-treated groups receiving 5 mg/kg 10 DCA, respectively. Diabetes was induced with streptozotocin (STZ) injections. Assessments included lipid peroxidation levels, plasma fibroblast growth factor-21 (FGF-21) transforming factor-beta (TGF-β) electrophysiological measurements, histological examination sciatic nerve, motor function tests. Treatment DCA significantly reduced malondialdehyde (MDA) indicating decreased peroxidation. Plasma TGF-β levels also lower groups, suggesting diminished inflammation. Conversely, FGF-21 elevated. Electrophysiological assessments revealed enhanced compound muscle action (CMAP) amplitudes distal latencies rats, indicative improved nerve conduction. Histopathological examinations showed perineural thickness nerves pointing fibrosis. Enhanced performance tests observed these implying strength capacity. The demonstrates that therapy reduces inflammation rat model DN, thereby ameliorating neuropathic symptoms. These results support as promising agent for treatment. Further research warranted explore clinical applications provide more detailed insights.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: March 26, 2025
Lactate has emerged as a key regulator in the tumor microenvironment (TME), influencing both progression and immune dynamics. As byproduct of aerobic glycolysis, lactate satisfies metabolic needs proliferating cells while reshaping TME to facilitate evasion. Elevated levels inhibit effector such CD8 + T natural killer cells, supporting immunosuppressive regulatory myeloid-derived suppressor thus fostering an environment. promotes epigenetic reprogramming, stabilizes hypoxia-inducible factor-1α, activates nuclear factor kappa B, leading further immunological dysfunction. In this review, we examined role suppression, treatment resistance. We also discuss promising therapeutic strategies targeting metabolism, including dehydrogenase inhibitors, monocarboxylate transporter neutralization methods, all which can restore function enhance immunotherapy outcomes. By highlighting recent advances, review provides theoretical foundation for integrating lactate-targeted therapies into clinical practice. highlight potential synergy between these current immunotherapeutic strategies, providing new avenues addressing TME-related challenges improving outcomes patients with cancer.
Language: Английский
Citations
0
Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 1, 2024
Language: Английский
Citations
1