A Microenvironment Dual‐Responsive Nano‐Drug Equipped with PD‐L1 Blocking Peptide Triggers Immunogenic Pyroptosis for Prostate Cancer Self‐Synergistic Immunotherapy

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(16)

Published: Jan. 25, 2023

Abstract Induction of immunogenic cell death (ICD) in tumor combined with immune checkpoint blockade (ICB) therapy is widely developed to improve the efficacy cancer immunotherapy. However, current ICD induced based on apoptosis, i.e., often restricted immunogenicity owing inflammatory quenching that occurs early apoptosis. Recently, pyroptosis demonstrated be a more efficient form, pyroptosis. The contents released during can powerfully activate immunogenicity. Herein, first, it lower doses epigenetic drug decitabine increase GSDME expression prostate (PCa) RM‐1 cells and successfully induce an apoptosis‐pyroptosis transition after photodynamic (PDT). Subsequently, microenvironment dual‐responsive nano‐drug equipped PD‐L1 blocking peptide (TSD@LSN‐D) for self‐synergistic poorly PCa model confirm powerful antitumor response evoked by TSD@LSN‐D not only effectively inhibit primary but also form long‐term memory prevent recurrence metastasis. To best authors’ knowledge, this work presents first concept promotes apoptosis–pyroptosis PDT through modulation. Furthermore, combination ICB opens new platform

Language: Английский

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Immunomodulation of wound healing leading to efferocytosis

Smart Medicine, Journal Year: 2024, Volume and Issue: 3(1)

Published: Jan. 31, 2024

Effectively eliminating apoptotic cells is precisely controlled by a variety of signaling molecules and phagocytic effect known as efferocytosis. Abnormalities in efferocytosis may bring about the development chronic conditions, including angiocardiopathy, inflammatory diseases autoimmune diseases. During wound healing, failure leads to collection apoptosis, release necrotic material wounds that are difficult heal. In addition traditional phagocytes-macrophages, other important cell species dendritic cells, neutrophils, vascular endothelial fibroblasts keratinocytes contribute wounding healing. This review summarizes how efferocytosis-mediated immunomodulation plays repair-promoting role providing new insights for patients suffering from various cutaneous wounds.

Language: Английский

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A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(12), P. 3229 - 3229

Published: Dec. 6, 2023

Inflammatory bowel disease (IBD) is a lifelong inflammatory immune mediated disorder, encompassing Crohn's (CD) and ulcerative colitis (UC); however, the cause specific pathogenesis of IBD yet incompletely understood. Multiple cytokines produced by different cell types results in complex functional networks that constitute highly regulated messaging network signaling pathways. Applying biological mechanisms underlying at single omic level, technologies genetic engineering enable quantification pattern released new insights into cytokine landscape IBD. We focus on existing literature dealing with biology pro- or anti-inflammatory interactions facilitate cell-based modulation system for inflammation. summarize main roles substantial related to homeostatic tissue functions remodeling IBD, which may be specifically valuable successful cytokine-targeted therapies via marketed products. Cytokines their receptors are validated targets multiple therapeutic areas, we review current strategies intervention developing therapies. New biologics have shown efficacy last few decades management IBD; unfortunately, many patients nonresponsive develop therapy resistance over time, creating need novel therapeutics. Thus, treatment options beyond immune-modifying anti-TNF agents combination expanding rapidly. Further studies needed fully understand response, cytokines, direct pathogenetic relevance regarding individually tailored, safe efficient targeted-biotherapeutics.

Language: Английский

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Immune Mechanisms in Hypertension

Hypertension, Journal Year: 2024, Volume and Issue: 81(8), P. 1659 - 1674

Published: June 17, 2024

It is now apparent that immune mediators including complement, cytokines, and cells of the innate adaptive system contribute not only to blood pressure elevation but also target organ damage occurs in response stimuli like high salt, aldosterone, angiotensin II, sympathetic outflow. Alterations vascular hemodynamic factors, microvascular pulsatility shear forces, lead release affect myeloid become potent antigen-presenting promote T-cell activation. Research past 2 decades has defined specific biochemical molecular pathways are engaged by these an emerging paradigm activation, products cells, reactive oxygen species, metalloproteinases act on further raise a feed-forward fashion. In this review, we will discuss pathophysiological events clinical interventions might prove effective quelling inflammatory process hypertension related cardiovascular diseases.

Language: Английский

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Thiamine deficiency aggravates experimental colitis in mice by promoting glycolytic reprogramming in macrophages

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Inflammatory bowel disease (IBD) is closely associated with immune dysfunction, where nutrient-mediated metabolic flux dictates cell fate and function. Thiamine a central water-soluble vitamin involved in cellular energy metabolism, its deficiency has been reported IBD patients. However, whether thiamine cause or consequence of pathogenesis remains unclear. The current study aimed to reveal the immunometabolic regulation macrophages underlying mechanism colitis development. was induced C57BL/6 mice bone marrow-derived (BMDMs), by administering thiamine-deficient diet/medium together pyrithiamine hydrobromide. frequency macrophage phenotypes their intracellular metabolism were detected using flow cytometry non-targeted metabolomics, respectively. aggravated ulcerative promoted infiltration proinflammatory M1 colonic lamina propria. Our mechanistic revealed that impaired pyruvate dehydrogenase (PDH) activity, thereby reprogramming glucose enhance glycolysis lactic acid accumulation macrophages. Using well-established PDH inhibitor (CPI-613) (galloflavin), we further demonstrated inhibition mimics, while lactate partially rescues, deficiency-induced experimental mice. provides evidence linking activation aggravation, suggesting monitoring status adjusting intake necessary protect against colitis.

Language: Английский

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The Pathogenicity and Synergistic Action of Th1 and Th17 Cells in Inflammatory Bowel Diseases

Inflammatory Bowel Diseases, Journal Year: 2022, Volume and Issue: 29(5), P. 818 - 829

Published: Sept. 27, 2022

Abstract Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn’s disease, are characterized by chronic idiopathic inflammation of gastrointestinal tract. Although the pathogenesis IBD remains unknown, intestinal immune dysfunction has been considered as core pathogenesis. In system, T helper 1 (Th1) Th17 cells indispensable for intestine homeostasis via preventing pathogenic bacteria invasion, regulating metabolism functions epithelial (IECs), promoting IEC self-renewal. However, during development IBD, Th1 acquire pathogenicity change from maintainer to destroyer mucosa. Because coexpressing interferon-γ interleukin-17A, with named cells. disease states, impair programs inducing apoptosis, recruiting cells, adhesion molecules expression IECs, differentiating cell molecule–specific interferon γ–positive Pathogenic induce injury triggering susceptibility genes IECs specifically killing IECs. addition, could cooperate colitis. The evidences patients animal models demonstrate that synergistic action occurs in aggravates mucosal inflammation. this review, we focused on discussed impact their onset IBD. We hoped provide some clues treating

Language: Английский

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The role of immune cells in different stages of atherosclerosis

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(6), P. 1129 - 1143

Published: Jan. 1, 2024

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of immune cells in intima arteries.Experimental and clinical evidence shows that both innate adaptive immunity orchestrate progression atherosclerosis.The heterogeneous nature within atherosclerosis lesions important.Studies utilizing high-dimensional mass spectrometry single-cell RNA sequencing leukocytes from atherosclerotic show diversity adaptability these cell subtypes.Their migration, compositional changes, phenotypic alterations, responses are key features throughout progression.Understanding how their subtypes affect atherogenesis would help to develop novel therapeutic approaches control progression.Precise targeting specific system components involved atherosclerosis, rather than broad suppression with anti-inflammatory agents, can more accurately regulate progress fewer side effects.In this review, we cover most recent advances field understand role various on its development.We focus complex network interaction between system.

Language: Английский

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TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101696 - 101696

Published: Aug. 23, 2024

Language: Английский

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Unravelling the anti-inflammatory mechanism of Allium cepa: an integration of network pharmacology and molecular docking approaches

Molecular Diversity, Journal Year: 2023, Volume and Issue: 28(2), P. 727 - 747

Published: March 3, 2023

Language: Английский

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PIM kinases regulate early human Th17 cell differentiation

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113469 - 113469

Published: Nov. 30, 2023

The serine/threonine-specific Moloney murine leukemia virus (PIM) kinase family (i.e., PIM1, PIM2, and PIM3) has been extensively studied in tumorigenesis. PIM kinases are downstream of several cytokine signaling pathways that drive immune-mediated diseases. Uncontrolled T helper 17 (Th17) cell activation associated with the pathogenesis autoimmunity. However, detailed molecular function PIMs human Th17 regulation yet to be studied. In present study, we comprehensively investigated how three simultaneously alter transcriptional gene during early differentiation. By combining triple knockdown bulk scRNA-seq approaches, found deficiency promotes expression key Th17-related genes while suppressing Th1-lineage genes. Further, modulate Th signaling, potentially via STAT1 STAT3. Overall, our study highlights inhibitory role differentiation, thereby suggesting their association autoimmune phenotypes.

Language: Английский

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