The combination of flaxseed lignans and PD-1/ PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 80, P. 101222 - 101222

Published: Feb. 28, 2025

Patients with breast cancer (BC) who benefit from the PD-1/PD-L1 inhibitor (PDi) is limited, necessitating novel strategies to improve immunotherapy efficacy of BC. Here we aimed investigate inhibitory effects flaxseed lignans (FL) on biological behaviors BC and evaluate roles FL in enhancing anticancer PDi. HPLC was used detect content enterolactone (ENL), bacterial transformation product FL. Transcript sequencing performed identified CD38 as a downstream target gene ENL. CD38-overexpressing cells were constructed cell proliferation, colony formation, wound healing transwell assays assess function ENL/CD38 axis vitro. Multiplexed immunohistochemistry (mIHC) CyTOF changes tumor immune microenvironment (TIM). 16S rDNA explore gut microbiota mice. A series vivo experiments conducted mechanisms converted ENL by administration inhibited progression malignant downregulating CD38, key associated immunosuppression blockade resistance. The mIHC assay revealed that enhanced CD3+, CD4+ CD8+ reduced F4/80+ TIM. confirmed regulatory combination PDi (FLcPDi) In addition, analysis demonstrated FLcPDi treatment significantly elevated abundance Akkermansia and, importantly, response mice treated antibiotics. FL/ENL/CD38 progression. modulating host immunity.

Language: Английский

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A review of non-classical MAPK family member, MAPK4: A pivotal player in cancer development and therapeutic intervention

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 271, P. 132686 - 132686

Published: May 25, 2024

Language: Английский

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Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids

Pharmacological Research, Journal Year: 2023, Volume and Issue: 199, P. 107033 - 107033

Published: Dec. 5, 2023

Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally mice following fecal microbiota transplantation from patients resistant ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In present study, ATB-treated C57BL/6 J received FMT with advanced NSCLC amenable αPD-1. Additionally, subcutaneous LLC cells were injected into mice. oral gavage and αPD-1 injection administered on days 3 9 after tumour inoculation. 16 S rRNA, metabolomics, flow cytometry utilized clarify of baicalin's relief immunosuppression. The results indicated administration enriched bacteria such as Akkermansia Clostridia_UCG-014, resulted in an increase SCFAs, which improved ratio PD-1+ (CD8+ T cell/Treg) promoted levels IFN-γ+ CD8+ TNF-α+ within microenvironment. conclusion, regulates metabolites gut improve balance circumvent resistance. This achieved through regulation short-chain fatty acids.

Language: Английский

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Genome- and Toxicology-Based Safety Assessment of Probiotic Akkermansia muciniphila ONE Isolated from Humans

Foods, Journal Year: 2024, Volume and Issue: 13(13), P. 1979 - 1979

Published: June 24, 2024

In this study, the genome of Akkermansia muciniphila ONE (designated AKK ONE) was sequenced, assembled, and analyzed. addition, safety strain further evaluated by toxicological studies. The results showed that is contained on a single chromosome with total length 2,817,524 bp an average GC content 55.48%. total, 2411, 1131, 1168, 1745, 1402 genes were annotated to NR, GO, KEGG, COG, SwissProt database, respectively. Potential resistance genes, adeF, tetW, ANT(3″)-IIa, aadA1 detected. sensitive ampicillin, ceftriaxone, cefotaxime, meropenem, tetracycline, chloramphenicol resistant moxifloxacin. No potential virulence-related PathogenFinder database analysis non-potential human pathogen. This had good gastroenteric fluid tolerance weak ability colonize gut. test item-related adverse effects observed in acute subchronic toxicity test. did not display mutagenic activity either. change hematological clinical biochemical parameters mice. weights organs affected treatment. These support safe for use as probiotic at dose 8.28 × 109 CFU/kg bw/day.

Language: Английский

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A ketogenic diet rich in fish oil is superior to other fats in preventing NNK-induced lung cancer in A/J mice

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 7, 2024

Given that ketogenic diets (KDs) are extremely high in dietary fat, we compared different fats KDs to determine which was the best for cancer prevention. Specifically, a Western and 15% carbohydrate diet seven KDs, containing either or enriched medium chain fatty acids (MCTs), milk fat (MF), palm oil (PO), olive (OO), corn (CO) fish (FO) their ability reduce nicotine-derived nitrosamine ketone (NNK)-induced lung mice. While all tested were more effective at reducing nodules than diet, FO-KD most nodules. Correlating with this, mice on had low blood glucose highest β-hydroxybutyrate level, lowest liver acid synthase/carnitine palmitoyl-1a ratio dramatic increase fecal Akkermansia. We found no damage induced by FO-KD, while of total cholesterol/HDL unchanged diets. conclude is superior other NNK-induced cancer, perhaps being skewing whole-body metabolism from dependence as an energy source.

Language: Английский

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The role of amino acid metabolism in autoimmune hepatitis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116452 - 116452

Published: March 18, 2024

Autoimmune hepatitis (AIH) is an inflammatory chronic liver disease with persistent and recurrent immune-mediated injury. The exact cause of AIH still not fully understood, but it believed to be primarily due abnormal activation the immune system, leading autoimmune injury caused by breakdown tolerance. Although pathogenesis remains unclear, recent studies have shown that abnormalities in amino acid metabolism play significant roles its development. These can lead remodeling metabolic processes, signaling pathways, responses, which may present new opportunities for clinical intervention AIH. In this paper, we first briefly outline progress clinically relevant research on AIH, focusing role specific (including glutamine, cysteine, tryptophan, branched-chain acids, etc.) their associated metabolites, as well related development Furthermore, discuss scientific issues remain resolved regarding metabolism, interventions, aim contributing future metabolism-based a target diagnosis treatment

Language: Английский

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Oral Akkermansia muciniphila Biomimetic Nanotherapeutics for Ulcerative Colitis Targeted Treatment by Repairing Intestinal Epithelial Barrier and Restoring Redox Homeostasis

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

The structural disruption of intestinal barrier and excessive reactive oxygen/nitrogen species (RONS) generation are two intertwined factors that drive the occurrence development ulcerative colitis (UC). Synchronously restoring mitigating excess RONS is a promising strategy for UC management, but its treatment outcomes still hindered by low drug accumulation retention in colonic lesions. Inspired intestine colonizing bacterium, we developed mucoadhesive probiotic Akkermansia muciniphila-mimic entinostat-loaded hollow mesopores prussian blue (HMPB) nanotherapeutic (AM@HMPB@E) UC-targeted therapy via repairing scavenging RONS. After oral administration, negatively charged AM@HMPB@E specifically bind to positively inflamed colon lesions electrostatic interactions muciniphila membrane-mediated bioadhesion mechanism. Subsequently, superoxide dismutase (SOD)-, catalase (CAT)-like HMPB eliminated RONS, thereby alleviating RONS-mediated inflammation epithelial damage. Meanwhile, UC-site locally released entinostat could repair damaged inhibiting endothelial cell apoptosis up-regulating expression tight junctions. Both vitro vivo results shown not only exhibited an exceptional site also demonstrated superior therapeutic efficacy compared first-line sulfasalazine, as evidenced longer colon, less rectal bleeding body weight loss. Collectively, our findings highlight clinical application prospects this synchronous treatment, offering paradigm rational design nanomedicine.

Language: Английский

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The landscape of ATF3 in tumors: metabolism, expression regulation, therapy approach, and open concerns

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107666 - 107666

Published: Feb. 1, 2025

Language: Английский

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Pasteurized Akkermansia muciniphila Timepie001 ameliorates DSS-induced ulcerative colitis in mice by alleviating intestinal injury and modulating gut microbiota

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 19, 2025

Akkermansia muciniphila (A. muciniphila), known as a next-generation probiotic, has been widely recognized for its beneficial effects in various metabolic diseases. While there is not much research whether live or pasteurized A. different on intestinal health. In the present study, strain of was isolated from healthy individuals, with and named Timepie001 Timepie001+, respectively. They were administered to dextran sulfate sodium-induced ulcerative colitis mice investigate their influences host The results showed that prophylactic supplementation alleviates symptoms by retarding weight loss, preserving tissue structure, modulating inflammatory cytokines (TNF-α, IL-1β), enhance colonic mucosal barrier upregulating expression tight junction protein Claudin-1. Interestingly, better effect compared muciniphila. Moreover, can regulates gut microbiome maintain homeostasis. This provides theoretical support widespread application postbiotics food industry.

Language: Английский

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Linking microbiome to cancer: A mini-review on contemporary advances

The Microbe, Journal Year: 2025, Volume and Issue: unknown, P. 100279 - 100279

Published: Feb. 1, 2025

Language: Английский

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