Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer DOI Creative Commons
Lei Li,

Hongbin Wang,

Shiyuan Zhang

et al.

International Journal of Surgery, Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Background: In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people’s attention. Statin may be potentially associated with a reduced risk breast cancer. Objective: To explore relationship between statin and cancer risk. And further potential role statins in adjuvant treatment Methods: Data for Mendelian randomization portion study were obtained from genome-wide association studies common cancers UK Biobank FinnGen Global Lipid Genetics Consortium’s low density lipoprotein (LDL). addition, impacts chemotherapy drugs on examined using both vitro vivo models, particular attention to expression levels immune checkpoint protein PD-L1 its suppress tumor growth. Results: about 3.8 million patients approximately 1.3 LDL-measuring individuals analyzed. Genetically proxied HMGCR inhibition (statins) was reduction ( P = 0.0005). experiments showed that lovastatin significantly inhibited paclitaxel-induced assisted paclitaxel suppressing cell Furthermore, combination therapy involving amplified CD8 + T-cell infiltration, bolstering their tumor-killing capacity enhancing efficacy. Conclusion: The utilization is correlated improved prognoses play facilitating transition cold hot tumors. Combination enhances activity leads better prognostic characteristics.

Language: Английский

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets DOI Creative Commons
Shaosen Zhang,

Xinyi Xiao,

Yonglin Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

Citations

55
The microbial landscape of colorectal cancer DOI
Maxwell T. White, Cynthia L. Sears

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 22(4), P. 240 - 254

Published: Oct. 4, 2023

Language: Английский

Citations

53
A Gpr35-tuned gut microbe-brain metabolic axis regulates depressive-like behavior DOI Creative Commons

Lingsha Cheng,

Haoqian Wu, Xiaoying Cai

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(2), P. 227 - 243.e6

Published: Jan. 9, 2024

Language: Английский

Citations

38
Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages DOI Creative Commons
Yuke Li, Qingxiang Li,

Ruoshui Yuan

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2719 - 2735

Published: Jan. 1, 2024

Aim: To elucidate dynamics and functions in colonic macrophage subsets, their regulation by Bifidobacterium breve (B.breve) its associated metabolites the initiation of colitis-associated colorectal cancer (CAC).Methods: Azoxymethane (AOM) dextran sodium sulfate (DSS) were used to create a CAC model.The tumor-suppressive effect B. variations subsets evaluated.Intestinal macrophages ablated determine role protective effects breve.Efficacious molecules produced identified non-targeted targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.The molecular mechanism was further verified murine bone marrow-derived (BMDMs), derived from human peripheral blood mononuclear cells (hPBMCs), demonstrated mice.Results: alleviated colitis symptoms, delayed tumorigenesis, promoted phenotypic differentiation immature inflammatory into mature homeostatic macrophages.On contrary, ablation intestinal largely annulled breve.Microbial analysis contents revealed enrichment probiotics depletion potential pathogens following supplementation.Moreover, indole-3-lactic acid (ILA) positively correlated with mice highly enriched culture supernatant breve.Also, addition ILA directly AKT phosphorylation restricted pro-inflammatory response BMDMs hPBMCs vitro.The abolished aryl hydrocarbon receptor (AhR) antagonist CH-223191 or inhibitor MK-2206.Furthermore, could protect against tumorigenesis regulating mice; AhR abrogated relieving tumorigenesis.Conclusion: breve-mediated tryptophan metabolism ameliorates precancerous milieu inhibit directing macrophages.

Language: Английский

Citations

21
The role of interleukin-17 in inflammation-related cancers DOI Creative Commons
Xingru Zhang, Bin Li, Lü Tian

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 21, 2025

Emerging evidence indicates a correlation between inflammation and the development progression of cancer. Among various inflammatory signals, interleukin-17 (IL-17) family cytokines serve as critical link IL-17 is highly versatile pro-inflammatory cytokine that plays pivotal role in host defense, tissue repair, pathogenesis diseases, cancer progression. During early stages tumorigenesis, signaling directly promotes proliferation tumor cells. Conversely, has been shown to exhibit antitumor immunity several models grafted subcutaneous tumors. Additionally, dynamic changes microbiome can influence secretion IL-17, thereby affecting development. The specific contingent upon its functional classification, spatiotemporal characteristics, stage In this review, we introduce fundamental biology expression profile receptors cancer, while also reviewing discussing recent advancements regarding pleiotropic effects mechanisms inflammation-related cancers. Furthermore, supplement our discussion with insights into by which impacts through interactions microbiota, explore implications therapy. This comprehensive analysis aims enhance understanding potential treatment.

Language: Английский

Citations

3
Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies DOI
Bo Zhao, Xinrong Hu, Weidong Wang

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

Citations

3
The human microbiome and cancer: a diagnostic and therapeutic perspective DOI Creative Commons
Shruthi Kandalai, Huapeng Li, Nan Zhang

et al.

Cancer Biology & Therapy, Journal Year: 2023, Volume and Issue: 24(1)

Published: July 27, 2023

Recent evidence has shown that the human microbiome is associated with various diseases, including cancer. The salivary microbiome, fecal and circulating microbial DNA in blood plasma have all been used experimentally as diagnostic biomarkers for many types of microbiomes present within local tissue, other regions, tumors themselves to promote restrict development progression cancer, most often by affecting cancer cells or host immune system. These microbes also impact efficacy therapies, radiation, chemotherapy, immunotherapy. Here, we review research advances focused on how these different facets why they are important clinical care It only better understanding roles play diagnosis, development, progression, treatment will be able catch treat early.

Language: Английский

Citations

38
Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis DOI Creative Commons
Guanqun Li, Liwei Liu, Tianqi Lu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 4, 2023

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis associated with pancreatic injury in HTGP the mechanism remains unclear. Here, we observe lower diversity gut absence beneficial bacteria patients. In a fecal transplantation mouse model, colonization from patients recruits neutrophils increases neutrophil extracellular traps (NETs) formation that exacerbates systemic inflammation. We find decreased abundance Bacteroides uniformis impairs taurine production IL-17 release colon triggers NETs formation. Moreover, or inhibits activation NF-κB signaling pathways which harness alleviate injury. Our findings establish roles endogenous uniformis-derived metabolic inflammatory products on suppressing release, provides potential insights ameliorating through modulation.

Language: Английский

Citations

35
Bacterial indole-3-lactic acid affects epithelium–macrophage crosstalk to regulate intestinal homeostasis DOI Creative Commons
Kaiyuan Yu, Qianqian Li,

Xuan Sun

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(45)

Published: Oct. 30, 2023

Tryptophan and its derivatives perform a variety of biological functions; however, the role specific mechanism many tryptophan in intestinal inflammation remain largely unclear. Here, we identified that an Escherichia coli strain ( Ec- TMU) isolated from feces tinidazole-treated individuals, indole-3-lactic acid (ILA) supernatant, decreased susceptibility mice to dextran sulfate sodium–induced colitis. TMU ILA contribute relief colitis by inhibiting production epithelial CCL2/7, thereby reducing accumulation inflammatory macrophages vitro vivo. Mechanistically, downregulates glycolysis, NF-κB, HIF signaling pathways via aryl hydrocarbon receptor, resulting CCL2/7 cells. Clinical evidence suggests fecal level is negatively correlated with progression indicator bowel diseases. These results demonstrate has potential regulate homeostasis modulating epithelium–macrophage interactions.

Language: Английский

Citations

35
Single‐Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging DOI Creative Commons
Chuanchuan Zhou, Qi Guo,

Jiayu Lin

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(4)

Published: Nov. 30, 2023

Abstract Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, aging‐related cellular molecular changes human ovaries that occur these years have not been elucidated. Here, single‐cell RNA sequencing (scRNA‐seq) of is performed from different childbearing ages reveals activation pyroptosis pathway increased age, mainly macrophages. The enrichment pyroptotic macrophages leads to switch tissue‐resident macrophage (TRM)‐involve immunoregulatory microenvironment young monocyte‐derived (MDM)‐involved proinflammatory middle‐aged ovaries. This remolded ovarian immuno‐microenvironment further promotes stromal cell senescence accelerated decline. hypothesis validated series animal experiments using GSDMD‐KO mice. In conclusion, work expands current understanding aging process by illustrating macrophage‐involved immune mechanism, has important implications for development novel strategies delay promote health.

Language: Английский

Citations

28