The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 29, 2024

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence mortality, deprives countless patients of health even life. According to global cancer statistics, there were an estimated 19.3 million new cases nearly 10 deaths in 2020, the age-standardized mortality rates 201.0 100.7 per 100,000, respectively. Although remarkable advancements have been made therapeutic strategies recently, overall prognosis remains optimistic. Consequently, are still many severe challenges be faced difficult problems solved therapy today. Epigallocatechin gallate (EGCG), natural polyphenol extracted from tea leaves, received much attention for antitumor effects. Accumulating investigations confirmed EGCG can inhibit tumorigenesis progression by triggering apoptosis, suppressing proliferation, invasion, migration, altering tumor epigenetic modification, overcoming chemotherapy resistance. Nevertheless, regulatory roles biomolecular mechanisms immune microenvironment, metabolic immunotherapy remain obscure. In this article, we summarized most recent updates about effects on microenvironment (TME), reprogramming, anti-cancer immunotherapy. The results demonstrated promote response cytotoxic lymphocytes dendritic cells (DCs), attenuate immunosuppression myeloid-derived suppressor (MDSCs) T (Tregs), tumor-promoting functions tumor-associated macrophages (TAMs), neutrophils (TANs), various stromal including cancer-associated fibroblasts (CAFs), endothelial (ECs), stellate cells, mesenchymal stem/stromal (MSCs). Additionally, suppress multiple reprogramming pathways, glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, nucleotide synthesis. Finally, EGCG, as immunomodulator checkpoint blockade, enhance immunotherapeutic efficacy may promising candidate conclusion, plays versatile TME which provides novel insights combined

Language: Английский

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Antioxidant and Anti-Inflammatory Effects of Vanillic Acid in Human Plasma, Human Neutrophils, and Non-Cellular Models In Vitro

Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 467 - 467

Published: Jan. 22, 2025

Vanillic acid (VA) is a dietary benzoic derivative, flavoring agent, and food stabilizer. In this study, the antioxidant anti-inflammatory potential of VA was explored in vitro ex vivo human immune cells non-cellular models. neutrophils, significantly downregulated fMLP-induced oxidative burst generation reactive oxygen species (ROS); it also suppressed release pro-inflammatory cytokines (TNF-α, IL-8) tissue-remodeling enzyme elastase-2 (ELA-2) stimulated with LPS fMLP+cytochalasin B. Additionally, showed good biocompatibility neutrophils peripheral blood mononuclear (PBMCs) across tested concentrations 1–50 µg/mL. Furthermore, at 1–5 μg/mL enhanced non-enzymatic capacity plasma (NEAC) prevented nitrative damage to proteins by protecting tyrosine moieties thiols from peroxynitrite. inhibited lipid peroxidation formation thiobarbituric acid-reactive substances (at 50 μg/mL) protein-bound carbonyls 5–50 peroxynitrite-treated plasma. tests, acted as hypochlorous hydrogen peroxide scavenger protein glycation, outperforming references Trolox aminoguanidine. Along existing data animal models studies on polyphenol intake, these results might support synergic role protection against chronic diseases related stress inflammation.

Language: Английский

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Dental stem cell dynamics in periodontal ligament regeneration: from mechanism to application

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 31, 2024

Periodontitis, a globally prevalent chronic inflammatory disease is characterized by the progressive degradation of tooth-supporting structures, particularly periodontal ligament (PDL), which can eventually result in tooth loss. Despite various clinical interventions available, most focus on symptomatic relief and lack substantial evidence supporting functional regeneration PDL. Dental stem cells (DSCs), with their homology mesenchymal cell (MSC) properties, have gained significant attention as potential avenue for PDL regeneration. Consequently, multiple therapeutic strategies been developed to enhance efficacy DSC-based treatments improve outcomes. This review examines mechanisms DSCs derivatives promote regeneration, explores diverse applications exogenous implantation endogenous regenerative technology (ERT) aimed at amplifying capacity DSCs. Additionally, persistent challenges controversies surrounding DSC therapies are discussed, alongside an evaluation limitations current research underlying innovative aim providing new insights future development. disease, represents major global public health concern, affecting proportion population standing leading cause loss adults. The (PDL) plays indispensable role maintaining health, its structural biological integrity crucial long-term prognosis tissues. It widely recognized cornerstone availability treatments, ranging from nonsurgical guided tissue (GTR) techniques, these methods shown limited success achieving meaningful As result, inability fully restore function underscores urgent need reconstructing this essential structure. Stem therapy, known immunomodulatory potential, offers promising approach repair. Their application marks paradigm shift treatment diseases, opening avenues However, much has primarily focused alveolar bone gingiva, hard soft tissues be more easily evaluated through visual assessment. complexity structure, coupled intricate interactions among cellular molecular components, presents scientific hurdles translating into practical applications. provides thorough exploration dynamics detailing origins, derived products, while also examining in-depth analysis research, landscape, acknowledging both progress made that remain bridging gap between laboratory findings implementation. Finally, continued investigation governing behavior optimization use diseases emphasized.

Language: Английский

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Targeting neutrophil elastase is a promising direction for future cancer treatment

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 15, 2024

Abstract Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil traps (NETs) through degranulation. In addition to participating in body's inflammatory response, NE also plays an important role cancer. It can promote tumor proliferation, migration, and invasion, induce epithelial-mesenchymal transition (EMT), change microenvironment (TME) progression. Concurrently, promotes systemic treatment resistance by inducing EMT. However, it selectively kill cancer cells attenuate development. Sivelestat specific inhibitor that be used perioperative period esophageal patients reduce incidence postoperative complications after esophagectomy. addition, combination sivelestat trastuzumab enhance efficacy human epidermal growth factor receptor 2(HER 2) positive breast patients. Meanwhile, targeting antibody domains fragments new way treat inflammation-related diseases. This review provides valuable insights into treatment. Additionally, we discuss challenges associated with clinical application sivelestat. By shedding light on promising potential NE, this contributes advancement strategies.

Language: Английский

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Immature forms of low density granulocytes are increased in acute myeloid leukemia and myelodysplastic syndromes

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 13, 2025

Neutrophils can promote or suppress tumor growth. These different immunological functions mirror a great heterogenicity of neutrophil maturation and activation status: low-density granulocytes (LDGs) normal-density neutrophils (NDNs). LDGs participate in immune dysregulation during autoimmune disorders with an activated phenotype, while NDNs might exert immunosuppressive activities. Here, we investigated variations distribution benign malignant hematological conditions using optimized 10-color flow cytometry staining for immunophenotyping the main circulating populations. A total 102 consecutive subjects diagnosed malignancies was enrolled by cytometry. We showed impaired subset myelodysplastic syndromes (MDS) acute myeloid leukemia (AML) patients compared to healthy individuals, intermediate mature significantly reduced, also displaying good diagnostic sensitivity MDS (AUC, 0.793 P = 0.0013; AUC, 0.7319 0.0109, respectively) AML 0.9059 0.0069; 0.9176 0.00057, respectively). In conclusion, LDG NDN subsets could be altered MDS, favor more immature forms, suggesting that emergency hemopoiesis first mechanism sustain peripheral blood counts, maintaining pro-inflammatory microenvironment.

Language: Английский

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Possible pharmacological targets and mechanisms of sivelestat in protecting acute lung injury

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 170, P. 108080 - 108080

Published: Jan. 29, 2024

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play central role releasing inflammatory mediators, elastase. Sivelestat selective and competitive inhibitor neutrophil Although its protective effects on attenuating ALI/ARDS have been confirmed in several models injury, clinical trials presented inconsistent results therapeutic efficacy. Therefore, this report, we used network pharmacology approach coupled with animal experimental validation to unravel concrete targets biological mechanisms sivelestat treating ALI/ARDS. bioinformatic analyses, found 118 against identified six hub genes essential for treatment namely ERBB2, GRB2, PTK2, PTPN11, ESR1, CCND1. We also that targeted expressed human microvascular endothelial cells after lipopolysaccharide (LPS) at 4 h (ICAM-1, PTGS2, RND1, BCL2A1, TNF, CA2, ADORA2A), 8 MMP1, BDKRB1 SLC40A1), 24 (ICAM-1). Further experiments showed was able attenuate LPS-induced ALI inhibiting overexpression ICAM-1, VCAM-1, PTGS2 increasing phosphorylation PTK2. Taken together, findings experimentative data indicate mainly focus early stage pharmacological modulation reaction, vascular cell apoptosis-related molecules.

Language: Английский

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Neutrophil diversity and function in health and disease

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

Published: Dec. 5, 2024

Abstract Neutrophils, the most abundant type of granulocyte, are widely recognized as one pivotal contributors to acute inflammatory response. Initially, neutrophils were considered mobile infantry innate immune system, tasked with immediate response invading pathogens. However, recent studies have demonstrated that versatile cells, capable regulating various biological processes and impacting both human health disease. Cytokines other active mediators regulate functional activity by activating multiple receptors on these thereby initiating downstream signal transduction pathways. Dysfunctions in disruptions neutrophil homeostasis been implicated pathogenesis numerous diseases, including cancer disorders, often due aberrant intracellular signaling. This review provides a comprehensive synthesis functions, integrating advancements this field. Moreover, it examines roles signaling pathways involved regulation activity. The pathophysiology diseases emerging therapeutic approaches targeting them also elaborated. addresses current limitations within field research, highlighting critical gaps knowledge warrant further investigation. In summary, seeks establish multidimensional model regulation, providing new perspectives for potential clinical applications research.

Language: Английский

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A comprehensive overview of investigational elastase inhibitors for the treatment of acute respiratory distress syndrome

Expert Opinion on Investigational Drugs, Journal Year: 2023, Volume and Issue: 32(9), P. 793 - 802

Published: Sept. 2, 2023

Introduction Excessive activity of neutrophil elastase (NE), the main enzyme present in azurophil granules cytoplasm, may cause tissue injury and remodeling various lung diseases, including acute (ALI)/acute respiratory distress syndrome (ARDS), which it is crucial to immune response inflammatory process. Consequently, NE a possible target for therapeutic intervention ALI/ARDS.

Language: Английский

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Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice

Science Advances, Journal Year: 2023, Volume and Issue: 9(43)

Published: Oct. 25, 2023

While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not studied. Diabetic Akita mice were crossed with either

Language: Английский

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CTC-neutrophil interaction: A key driver and therapeutic target of cancer metastasis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117474 - 117474

Published: Sept. 23, 2024

Language: Английский

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