Unveiling the role of regulatory T cells in the tumor microenvironment of pancreatic cancer through single-cell transcriptomics and in vitro experiments

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 11, 2023

In order to investigate the impact of Treg cell infiltration on immune response against pancreatic cancer within tumor microenvironment (TME), and identify crucial mRNA markers associated with cells in cancer, our study aims delve into role anti-tumor cancer.The ordinary transcriptome data for this was sourced from GEO TCGA databases. It analyzed using single-cell sequencing analysis machine learning. To assess level tissues, we employed CIBERSORT method. The identification genes most closely accomplished through implementation weighted gene co-expression network (WGCNA). Our involved various quality control methods, followed by annotation advanced analyses such as trajectory communication elucidate microenvironment. Additionally, categorized two subsets: Treg1 favorable prognosis, Treg2 poor based enrichment scores key genes. Employing hdWGCNA method, these subsets critical signaling pathways governing their mutual transformation. Finally, conducted PCR immunofluorescence staining vitro validate identified genes.Based results analysis, observed significant Subsequently, utilizing WGCNA learning algorithms, ultimately four cell-related (TRGs), among which exhibited correlations occurrence progression cancer. Among them, CASP4, TOB1, CLEC2B were poorer prognosis patients, while FYN showed a correlation better prognosis. Notably, differences found HIF-1 pathway between These conclusions further validated experiments.Treg played microenvironment, presence held dual significance. Recognizing characteristic vital understanding limitations cell-targeted therapies. FYN, close associations infiltrating suggesting involvement functions. Further investigation warranted uncover mechanisms underlying associations. emerged contributing duality cells. Targeting could potentially revolutionize existing treatment approaches

Язык: Английский

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Unveiling the Association between HPV and Pan-Cancers: A Bidirectional Two-Sample Mendelian Randomization Study

Cancers, Год журнала: 2023, Номер 15(21), С. 5147 - 5147

Опубликована: Окт. 26, 2023

More and more studies have focused on the associations between human papillomavirus (HPV) infection pan-cancers. However, current evidence is largely based retrospective studies, which are susceptible to confounding factors do not enable establishment of causal relationships.

Язык: Английский

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Deciphering a Prognostic Signature Based on Soluble Mediators Defines the Immune Landscape and Predicts Prognosis in HNSCC

Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(3)

Опубликована: Март 22, 2024

Background: The study on Head and Neck Squamous Cell Carcinoma (HNSCC), a prevalent aggressive form of head neck cancer, focuses the often-overlooked role soluble mediators. objective is to leverage transcriptome-based risk analysis utilizing mediator-related genes (SMRGs) provide novel insights into prognosis immunotherapy efficacy in HNSCC patients. Methods: We analyzed expression prognostic significance 10,859 SMRGs using 502 44 normal samples from TCGA-HNSC cohort Cancer Genome Atlas (TCGA). were divided training test sets 7:3 ratio, with an additional external validation 40 tumor International Consortium (ICGC). Key differentially expressed (DEGs) identified through univariate Lasso-Cox regression analyses. A model based 20 was developed Lasso multivariate Cox regression. assessed clinical outcomes immune status high-risk (HR) low-risk (LR) patients BEST databases single-sample Gene Set Enrichment Analysis (ssGSEA). Results: crucial predicting HNSCC, SMRG signature emerging as independent indicator. Patients classified HR group exhibited poorer compared those LR group. nomogram, integrating characteristics scores, demonstrated substantial value. Immunotherapy appeared be more effective group, possibly attributed enhanced infiltration checkpoints. Conclusions: mediator-associated offers fresh perspective for assessing pre-immune showcases robust predictive capabilities. This innovative approach holds significant promise advancing field precision immuno-oncology research, providing valuable personalized treatment strategies HNSCC.

Язык: Английский

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Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 28, 2025

Background Osteosarcoma (OS) is one of the most common primary malignant bone tumors, primarily originating from mesenchymal tissue. It notorious for its high invasiveness, disability rate, mortality and poor prognosis. In metastatic destruction can promote cancer progression, which closely related to osteoclast activation imbalance between osteoblasts osteoclasts. A large number studies confirmed that osteoclasts are an important part OS, play active role in destroying homeostasis promoting progress OS. Therefore, we conducted a detailed study at single cell level, aiming find new OS therapeutic targets prevent tumor progression local spread. Methods We analyzed single-cell sequencing data patients usedMonocle2, Cytotrace, Slingshot software analyze pseudo-sequential trajectory during progression. CellChat was used reveal communication cells. PySCENIC identify transcription factors Finally, further demonstrated results by RT-qPCR analysis, CCK-8 assay, wound healing Transwell etc. Results Through analysis identified highly specific subgroup, C2MKI67+ Osteoclast. The key signaling pathway APP top 1 factor PPARG this subgroup played essential roles proliferation differentiation. Given pivotal speculated these pathways could emerge as novel targets, offering innovative strategies treatment. Conclusion This enhanced our understanding through scRNA-seq. Furthermore, discovered amplifies proliferation, resulting excessive resorption degradation matrix, thereby creating favorable environment growth. By innovatively targeting PPARG, it affected thus progression; work offered insights directions clinical treatment patients.

Язык: Английский

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Disulfidptosis as a key regulator of glioblastoma progression and immune cell impairment

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 30, 2025

Background Glioblastoma, associated with poor prognosis and impaired immune function, shows potential interactions between newly identified disulfidptosis mechanisms T cell exhaustion, yet these remain understudied. Methods Key genes were using Lasso regression, followed by multivariate analysis to develop a prognostic model. Single-cell pseudotemporal explored T-cell exhaustion (Tex) signaling in differentiation. Immune infiltration was assessed via ssGSEA, while transwell assays immunofluorescence examined the effects of disulfidptosis-Tex on glioma behavior response. Results Eleven found critical for glioblastoma survival outcomes. This gene set underpinned model predicting patient prognosis. showed high activity endothelial cells. Memory populations linked genes. SMC4 inhibition reduced LN299 migration increased chemotherapy sensitivity, decreasing CD4 CD8 activation. Conclusions Disulfidptosis-Tex are pivotal progression interactions, offering new avenues improving anti-glioblastoma therapies through modulation exhaustion.

Язык: Английский

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A case–control study based on the National Health and Nutrition Examination Survey to evaluate the effects of human papilloma virus on bone health in women

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 7, 2025

Human papillomavirus (HPV) infection and osteoporosis (OP) are global health concerns, with higher prevalence observed in women compared to men. However, the impact of HPV on bone remains uncertain. This case–control study utilized data from National Health Nutrition Examination Survey (NHANES). Comparable datasets were created using nearest neighbor propensity score matching (PSM) at a ratio 1:1. The association between mineral density (BMD) was analyzed Welch two-sample t-test. Furthermore, linear mixed models employed for validation purposes. Restricted cubic spline (RCS) analysis Kendall's tau-b tests performed explore effect different types BMD. Individuals (mean age 38.11 ± 11.32 years) had lower BMD femur lumbar spine uninfected individuals 37.92 11.42 years). RCS revealed that an increasing number cooccurring associated Specifically, four negatively BMD, while 14 Additionally, 53, 59, 89 exhibited effects both is decrease co-infection multiple implies even Appropriately designed trials needed determine if interventions targeted preventing can have protective

Язык: Английский

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Mini-review on the therapeutic vaccines targeting chronic infectious diseases: Evaluation system of therapeutic vaccines targeting HPV and EBV-related cancers

Human Vaccines & Immunotherapeutics, Год журнала: 2025, Номер 21(1)

Опубликована: Фев. 16, 2025

Chronic infectious diseases are threatening human health today, and their public severity is increasing. The efficacy issues of drugs the increase in drug-resistant pathogens require new response strategies for chronic diseases, therapeutic vaccines have recently been proposed as an effective alternative. However, research on still relatively underdeveloped. To solve this problem, accurate understanding status challenge at hand targeting needed. In present review, we provide overview latest trends summarize development currently undergoing clinical research, focusing cases papillomavirus (HPV) Epstein-Barr virus (EBV) representative examples. We highlight importance standard methods evaluation vaccine, cell-mediated immune response, which might accelerate vaccine development.

Язык: Английский

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Trichomonas vaginalis adhesion protein 33 (TvAP33) promotes HPV infection by upregulating the expression of HPV membrane receptor molecules

Acta Tropica, Год журнала: 2025, Номер unknown, С. 107578 - 107578

Опубликована: Март 1, 2025

Язык: Английский

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Targeting the interplay between human papillomavirus oncoproteins and hedgehog signaling: assessment of chemopreventive potential of carvacrol in cervical cancer

3 Biotech, Год журнала: 2025, Номер 15(4)

Опубликована: Март 5, 2025

Язык: Английский

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Metformin-induced E6/E7 inhibition prevents HPV-positive cancer progression through p53 reactivation

Anti-Cancer Drugs, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

The human papillomavirus (HPV) is implicated in multiple lethal cancers, although it more sensitive to certain therapies than HPV-negative cancers. Therefore, the development of targeted therapeutic strategies imperative. HPV oncogenes E6/E7 are ideal targets for HPV-positive cancer, but there no clinical that have been proven effectively target E6/E7. Notably, metformin significantly inhibits expression; however, underlying mechanism and potential remain unclear, limiting its translation. Cell Counting Kit-8, ethynyl-2′-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated Nick end labeling assays were conducted evaluate effects on cell viability, proliferation, apoptosis. Quantitative real-time PCR, western blotting, immunofluorescence performed determine changes p53 expression levels following treatment. Patient-derived organoids in-vivo xenograft models constructed anticancer activity against cancer. Our research demonstrated enhanced sensitivity cancer cells metformin. Mechanistic studies revealed exerts by inhibiting expression, which associated with reactivation. Furthermore, we substantiated patient-derived tumor models. study focused responsiveness metformin, highlighting as a strategy

Язык: Английский

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