International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114671 - 114671
Published: April 19, 2025
Language: Английский
Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 219 - 219
Published: Jan. 31, 2024
Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV from fatal disease into manageable chronic condition, definitive cure elusive. One of the key features is immune activation and inflammation, are strongly associated with, predictive of, progression, even patients successfully treated with suppressive ART. inflammation characterized by persistent cell metabolic dysregulation, cellular exhaustion dysfunction. This review aims summarize current knowledge interplay between metabolism, T dysfunction infection, also discusses use humanized mice models study pathogenesis develop novel therapeutic strategies.
Language: Английский
Citations
20
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)
Published: April 29, 2024
Abstract The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC remains limited, underlying mechanisms are still uncertain. Therefore, this study aimed characterize effects ATO By evaluating susceptibilities human murine cell lines treatment, we discovered that cells exhibited range sensitivity highlighting their heterogeneity. A gene signature comprising 265 genes was identified distinguish ATO-sensitive from ATO-insensitive cells. According signature, patients have also been classified differential features response. Our results showed induced reactive oxygen species (ROS) accumulation activation multiple death modalities, necroptosis ferroptosis, Meanwhile, elevated immunogenicity observed Similar were not We reported mitochondrial injury mtDNA release into cytoplasm tumors. This subsequently activated cGAS-STING-IFN axis, facilitating CD8 + T infiltration activation. found IFN pathway PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted anti-tumor response In summary, our data indicate heterogeneous responses exist significantly induces immunogenic (ICD) activates tumor-derived mtDNA-STING-IFN axis. These findings may offer new perspective on clinical warrant further study.
Language: Английский
Citations
10
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 7, 2025
The inflammatory responses from synovial fibroblasts and macrophages the mitochondrial dysfunction in chondrocytes lead to oxidative stress, disrupt extracellular matrix (ECM) homeostasis, accelerate deterioration process of articular cartilage osteoarthritis (OA). In recent years, it has been proposed that mesenchymal stromal cells (MSC) transfer their functional mitochondria damaged response cellular becoming one mechanisms underpinning therapeutic effects. Therefore, we hypothesize a novel cell-free treatment for OA could involve direct transplantation, restoring both homeostasis. Mitochondria were isolated Umbilical Cord (UC)-MSC (Mito-MSC) characterized based on morphology, phenotype, functions, ability be internalized by different cells. Furthermore, transcriptional changes following uptake evaluated using an Affymetrix analysis, Lastly, dose dependence efficacy, biodistribution immunogenicity Mito-MSC assessed vivo, through intra-articular injection male C57BL6 mice collagenase-induced (CIOA) model. Our findings demonstrate integrity efficiently transferred into chondrocytes, macrophages, fibroblasts. Moreover, transcriptomic analysis showed upregulation genes involved stress such as DNA reparative machinery antiviral responses. Finally, transplantation yielded significant reductions joint mineralization, hallmark progression, well improvements OA-related histological signs, with lower exhibiting better efficacy. was detected within knee up 24 h post-injection without eliciting CIOA mice. Collectively, our results reveal derived MSC are key retained generating immune mitigating degradation OA, probably restorative effect triggered chondrocytes.
Language: Английский
Citations
1
Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 258, P. 155330 - 155330
Published: April 26, 2024
Language: Английский
Citations
6
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 275, P. 116638 - 116638
Published: June 28, 2024
Language: Английский
Citations
5
Advanced Science, Journal Year: 2024, Volume and Issue: unknown
Published: July 14, 2024
Interferons (IFNs) activate JAK-STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (β) II (γ) IFNs are shown that can the transcription factor IRF3 in parallel with STAT1. IRF3-deficiency impairs of a subset induced by IFN-β IFN-γ. Mechanistically, IFN-induced activation is dependent on cGAS-STING-TBK1 axis. Both IFN-γ cause mitochondrial DNA release into cytosol. In addition, JAK1-mediated tyrosine phosphorylation cGAS at Y214/Y215, which essential its binding activity signaling. Furthermore, deficiency cGAS, STING, or IFN-β- IFN-γ-mediated antiviral antitumor activities. The findings reveal novel pathway canonical STAT1/2 triggered provide an explanation pleiotropic roles cGAS-STING-IRF3 axis defense.
Language: Английский
Citations
5
Cancer Letters, Journal Year: 2025, Volume and Issue: 617, P. 217615 - 217615
Published: March 6, 2025
Language: Английский
Citations
0
Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)
Published: March 12, 2025
Abstract The cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) signaling pathway plays a crucial role in activating innate and specific immunity anti-tumor immunotherapy. As the major infiltrating cells tumor microenvironment (TME), tumor-associated macrophages (TAMs) could be polarized into either M1 or pro-tumor M2 types based on various stimuli. Accordingly, targeted reprogramming TAMs to restore immune balance shows promise as an effective strategy. In this review, we aim target cGAS-STING for enhance We investigated double-edged sword effects of regulating TME. regulative roles its impact TME were further revealed. More importantly, several strategies targeting designed enhancing Taken together, might promising strategy
Language: Английский
Citations
0
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116690 - 116690
Published: May 7, 2024
Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific supportive due to severity clinical course AP, which can fluctuate rapidly unpredictably. Mitochondria, cellular power plant produce energy, are involved in a variety physiological or pathological activities human body. There growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role pathogenesis progression AP. With pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding receptors, activating downstream molecules releasing inflammatory factors. This review focuses on possible interaction between AP mtDAMPs, include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) succinate, focus experimental research potential therapeutic targets practice. Preventing diminishing release targeting receptors might have progression.
Language: Английский
Citations
4
Experimental Neurology, Journal Year: 2024, Volume and Issue: 382, P. 114950 - 114950
Published: Sept. 13, 2024
Language: Английский
Citations
4