Virology, Journal Year: 2024, Volume and Issue: 600, P. 110266 - 110266
Published: Oct. 18, 2024
Language: Английский
Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 231 - 231
Published: Jan. 19, 2025
DNA damage repair (DDR) plays a key role in maintaining genomic stability and developing inflammatory bowel disease (IBD). However, no report about the causal association between DDR IBD exists. Whether DDR-related genes are precise to etiology remains unclear. Herein, we employed multi-omics summary data-based Mendelian randomization (SMR) approach ascertain potential effects of IBD. Methods: Summary statistics from expression quantitative trait loci (eQTL), methylation QTL (mQTL), protein (pQTL) on European descent were included. The GWAS summarized data for its two subtypes, Crohn’s (CD) ulcerative colitis (UC), acquired FinnGen study. We elected genetic variants located within or near 2000 cis, which closely associated with gene changes. Variants selected as instrumental variables (IVs) assessed causality subtypes using both SMR two-sample MR (TSMR) approaches. Colocalization analysis was evaluate whether single variant simultaneously influences traits, thereby validating pleiotropy hypothesis. Results: identified seven (Arid5b, Cox5a, Erbb2, Ube2l3, Gpx1, H2bcl2, Mapk3), 33 genes, proteins (CD274 FCGR2A) all causally subtypes. Beyond causality, integrated mQTL-eQTL conducted druggability values. found that Erbb2 Gpx1 significantly impacted their levels offering insights into regulatory mechanisms risk Meanwhile, CD247 FCGR2A could serve targets pharmacological interventions Conclusions: Our study demonstrates based data-driven MR. Moreover, targets.
Language: Английский
Citations
1
Advanced Science, Journal Year: 2024, Volume and Issue: 11(40)
Published: July 19, 2024
Abstract The success of immunotherapy for cancer treatment is limited by the presence an immunosuppressive tumor microenvironment (TME); Therefore, identifying novel targets to that can reverse this TME and enhance efficacy essential. In study, enrichment analysis based on publicly available single‐cell bulk RNA sequencing data from gastric patients are conducted, found tumor‐intrinsic interferon (IFN) plays a central role in regulation. results shows KDM3A over‐expression suppresses IFN response inhibits KDM3A, either genomically or pharmacologically, which effectively promotes responses activating endogenous retroviruses (ERVs). ablation reconfigures dsRNA‐MAVS‐IFN axis modulating H3K4me2, enhancing infiltration function CD8 T cells, simultaneously reducing regulatory resulting reshaped vivo. addition, combining anti‐PD1 therapy with inhibition inhibited growth. conclusions, study highlights as potential target remodeling enhancement antitumor immunity through regulation ERV‐MAVS‐IFN axis.
Language: Английский
Citations
4
MedComm, Journal Year: 2024, Volume and Issue: 5(11)
Published: Oct. 31, 2024
DNA damage response (DDR) pathway is the coordinated cellular network dealing with identification, signaling, and repair of damage. It tightly regulates cell cycle progression promotes to minimize daughter cells. Key proteins involved in DDR are frequently mutated/inactivated human cancers promote genomic instability, a recognized hallmark cancer. Besides being an intrinsic property tumors, also represents unique therapeutic opportunity. Indeed, inhibition expected delay repair, causing persistent unrepaired breaks, interfere progression, sensitize cancer cells several DNA-damaging agents, such as radiotherapy chemotherapy. In addition, defects have been shown render these more dependent on remaining pathways, which could be targeted very specifically (synthetic lethal approach). Research over past two decades has led synthesis testing hundreds small inhibitors against key proteins, some antitumor activity cancers. parallel, search for synthetic lethality interaction broadening use inhibitors. this review, we discuss state-of-art ataxia-telangiectasia mutated, ataxia-telangiectasia-and-Rad3-related protein, checkpoint kinase 1, Wee1 Polθ inhibitors, highlighting results obtained ongoing clinical trials both monotherapy combination chemotherapy radiotherapy.
Language: Английский
Citations
4
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: April 15, 2025
Cancer immunotherapy aims to harness the body's own immune system for effective and long-lasting elimination of malignant neoplastic tissues. Owing advance in understanding cancer pathology immunology, many novel strategies enhancing immunological responses against various cancers have been successfully developed, some translated into excellent clinical outcomes. As one promising strategy next generation immunotherapies, activating multi-cellular network (MCN) within tumor microenvironment (TME) deploy multiple mechanisms action (MOAs) has attracted significant attention. To achieve this effectively safely, delivering or pleiotropic therapeutic cargoes targeted sites cancerous tissues, cells, intracellular organelles is critical, which numerous nanocarriers developed leveraged. In review, we first introduce payloads categorized according their predicted functions physicochemical structures forms. Then, nanocarriers, along with unique characteristics, properties, advantages, limitations, are introduced notable recent applications immunotherapy. Following discussions on targeting strategies, a summary each nanocarrier matching suitable provided comprehensive background information designing regimens.
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: April 29, 2025
Language: Английский
Citations
0
PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e19402 - e19402
Published: May 2, 2025
DNA repair is a hierarchically organized, spatially and temporally regulated process involving numerous factors that respond to various types of damage. Despite decades research, the mechanisms by which these are recruited depart from sites have been subject intrigue. Recent advancements in field increasingly highlighted role phase separation as critical facilitator efficiency repair. This review emphasizes how enhances concentration coordination at damage sites, optimizing efficiency. Understanding dysregulation can impair alter nuclear organization, potentially leading diseases such cancer neurodegenerative disorders, crucial. manuscript provides comprehensive understanding pivotal repair, sheds light on current suggests potential future directions for research therapeutic interventions.
Language: Английский
Citations
0
Vaccines, Journal Year: 2025, Volume and Issue: 13(5), P. 496 - 496
Published: May 4, 2025
Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Conventional therapies are frequently limited by tumor heterogeneity and the immunosuppressive microenvironment (TME). Dendritic cells (DCs), central to orchestrating antitumor immunity, have become key targets for HCC immunotherapy. This review examines biological functions DC subsets (cDC1, cDC2, pDC, moDC) their roles in initiating modulating immune responses against HCC. We detail mechanisms underlying impairment within TME, including suppression regulatory T (Tregs), myeloid-derived suppressor (MDSCs), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs). Additionally, we discuss novel DC-based therapeutic strategies, such as vaccines designed enhance antigen presentation cell activation. Combining with checkpoint inhibitors (ICIs), PD-1/PD-L1 CTLA-4 blockers, demonstrates synergistic effects that can overcome evasion improve clinical outcomes. Despite progress, challenges related subset heterogeneity, TME complexity, patient variability require further optimization personalization therapies. Future research should focus on refining these leveraging advanced technologies like genomic profiling artificial intelligence, maximize efficacy revolutionize treatment. By restoring function reprogramming immunotherapy holds immense potential transform management survival.
Language: Английский
Citations
0
Virology, Journal Year: 2024, Volume and Issue: 600, P. 110266 - 110266
Published: Oct. 18, 2024
Language: Английский
Citations
1