Dissecting macrophage heterogeneity and kaempferol in lung adenocarcinoma: a single-cell transcriptomic approach and network pharmacology

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 30, 2025

Lung adenocarcinoma (LUAD) is a leading form of non-small cell lung cancer characterized by complex tumor microenvironment (TME) that influences disease progression and therapeutic response. Tumor-associated macrophages (TAMs) within the TME promote tumorigenesis evasion immune surveillance, though their heterogeneity poses challenges in understanding roles targeting. Additionally, traditional Chinese medicine (TCM) offers potential anti-cancer agents could modulate landscape. We conducted single-cell RNA sequencing (scRNA-seq) on LUAD samples, performing an in-depth analysis macrophage populations expression signatures. Network pharmacology was used to identify TCM components with TAM-modulatory effects, focusing Astragalus membranaceus. Pseudotime trajectory analysis, immunofluorescence staining, vitro assays examined functional TAMs effects selected compounds polarization. Our scRNA-seq identified notable among macrophages, revealing predominant M2-like phenotypes TAMs. highlighted active ingredients, including quercetin, isorhamnetin, kaempferol, targeting genes related function. Survival implicated AHSA1, CYP1B1, SPP1, STAT1 as prognostically significant factors. Further experiments demonstrated kaempferol's efficacy inhibiting M2 polarization, underlining selective influence TAM functionality. This study delineates diverse landscape suggests pivotal role for TAM-mediated immunosuppression. Kaempferol, from TCM, emerges influential agent capable altering potentially enhancing anti-tumoral immunity. These findings underscore translational integrating TCM-derived into immunotherapeutic strategies LUAD.

Language: Английский

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Advances in nucleic acid delivery strategies for diabetic wound therapy

Journal of Clinical & Translational Endocrinology, Journal Year: 2024, Volume and Issue: 37, P. 100366 - 100366

Published: Aug. 30, 2024

In recent years, the prevalence of diabetic wounds has significantly increased, posing a substantial medical challenge due to their propensity for infection and delayed healing. These not only increase mortality rates but also lead amputations severe mobility issues. To address this, advancements in bioactive molecules such as genes, growth factors, proteins, peptides, stem cells, exosomes into targeted gene therapies have emerged preferred strategy among researchers. Additionally, integration photothermal therapy (PTT), nucleic acid, therapy, along with 3D printing technology layer-by-layer (LBL) self-assembly approach, shows promise wound treatment. Effective delivery small interfering RNA (siRNA) relies on vectors. This review provides an in-depth exploration pathophysiological characteristics observed wounds, encompassing diminished angiogenesis, heightened levels reactive oxygen species, impaired immune function. It further examines acid delivery, advanced drug systems, techniques, negative pressure (NPWT), printing, hyperbaric ongoing clinical trials. Through research insights, this presents innovative strategies aimed at augmenting multifaceted management thus paving way enhanced therapeutic outcomes future.

Language: Английский

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The Role of the Large T Antigen in the Molecular Pathogenesis of Merkel Cell Carcinoma

Genes, Journal Year: 2024, Volume and Issue: 15(9), P. 1127 - 1127

Published: Aug. 27, 2024

The large T antigen (LT) of the Merkel cell polyomavirus (MCPyV) is crucial for carcinoma (MCC), a rare but very aggressive form neuroendocrine skin cancer. clonal integration MCPyV DNA into host genome signature event this malignancy. resulting expression oncogenes, including small (sT) and truncated LT (truncLT), directly contribute to carcinogenesis. truncation C-terminus prevents virus from replicating due loss origin binding domain (OBD) helicase domain. This precludes cytopathic effects that would lead damage ultimately death. At same time, LxCxE motif in N-terminus retained, allowing truncLT bind retinoblastoma protein (pRb), cellular tumor suppressor. continuously inactivated pRb promotes proliferation development. exerts several classical functions an oncogene: altering cycle, suppressing innate immune responses viral DNA, causing escape, shifting metabolism favor cancer cells. Given its central role MCC, major target therapeutic interventions with novel approaches, such as checkpoint inhibition, cell-based immunotherapy, vaccines.

Language: Английский

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Generic and Queryable Data Integration Schema for Transcriptomics and Epigenomics studies

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 4232 - 4241

Published: Nov. 19, 2024

Language: Английский

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The Role of Non-coding RNAs in Tumorigenesis, Diagnosis/Prognosis, and Therapeutic Strategies for Cutaneous Melanoma

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 79 - 107

Published: Dec. 19, 2024

Language: Английский

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