A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages DOI Creative Commons

Atsadang Boonmee,

Salisa Benjaskulluecha,

Patipark Kueanjinda

и другие.

Epigenetics & Chromatin, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 29, 2024

To avoid exaggerated inflammation, innate immune cells adapt to become hypo-responsive or "tolerance" in response successive exposure stimuli, which is a part of memory. Polycomb repressive complex 2 (PRC2) mediates the transcriptional repression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3) but little known about its role lipopolysaccharide (LPS)-induced tolerance macrophages. We examined unexplored roles EED, component PRC2, LPS tolerant In Eed KO macrophages, significant reduction H3K27me3 and increased active mark, H3K27ac, was observed. macrophages exhibited dampened pro-inflammatory cytokine productions (TNF-α IL-6) while increasing non-tolerizable genes upon tolerance. Pharmacological inhibition EED also reduced TNF-α IL-6 during Mechanistically, tolerized failed increase glycolytic activity. RNA-Seq analyses revealed that hallmarks hypoxia, TGF-β, Wnt/β-catenin signaling were enriched Among upregulated genes, promoter Runx3 found be associated with EED. Silencing partially rescued Enrichment decreased subset are indicating direct regulatory PRC2 on such genes. Motif enrichment analysis identified ETS family transcription factor binding sites absence Our results provided mechanistic insight into how via regulates epigenetically silencing play crucial as those TGF-β/Runx3 axis.

Язык: Английский

Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy DOI Open Access
Nada Oršolić, Maja Jazvinšćak Jembrek

Nutrients, Год журнала: 2024, Номер 16(21), С. 3741 - 3741

Опубликована: Окт. 31, 2024

Conventional cancer treatments include surgical resection, chemotherapy, hyperthermia, immunotherapy, hormone therapy, and locally targeted therapies such as radiation therapy. Standard often require the use of multiple agents, which can activate nuclear factor kappa B (NF-κB) in tumor cells, leading to reduced cell death increased drug resistance. Moreover, agents also contributes added toxicity, resulting poor treatment outcomes. Cancer cells gradually develop resistance almost all chemotherapeutics through various mechanisms, efflux, alterations metabolism transport, changes signal transduction pathways, enhanced DNA repair capacity, evasion apoptosis, mutations, reactivation targets, interaction with microenvironment, cell-stroma interactions, epithelial–mesenchymal transition (EMT)-mediated chemoresistance, epigenetic modifications, metabolic alterations, effect stem (CSCs). Developing new strategies improve chemotherapy sensitivity while minimizing side effects is essential for achieving better therapeutic outcomes enhancing patients’ quality life. One promising approach involves combining conventional propolis its flavonoids. These natural compounds may enhance response reducing toxicity. Propolis components sensitize chemotherapeutic likely by inhibiting NF-κB activation, reprogramming tumor-associated macrophages (TAMs; an M2-like phenotype), thereby release matrix metalloproteinase (MMP)-9, cytokines, chemokines, vascular endothelial growth (VEGF). By TAMs, overcome EMT-mediated disrupt crosstalk between CSCs, inhibit maintenance stemness, reverse acquired immunosuppression, thus promoting antitumor mediated cytotoxic T-cells. This review highlights potential flavonoids modulate responsiveness modalities. The evidence suggests that novel incorporating could be developed positive cytotoxicity peripheral blood leukocytes, liver, kidney cells. Therefore, polyphenolic/flavonoid hold combination clinical types cancers.

Язык: Английский

Процитировано

6
Epigenetic modifications in bladder cancer: crosstalk between DNA methylation and miRNAs DOI Creative Commons
Wei Li,

Peiyue Luo,

Qi Chen

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 5, 2025

Bladder cancer (BC) is a malignant tumor characterized by high incidence of urinary system diseases. The complex pathogenesis BC has long been focal point in medical research. With the robust development epigenetics, crucial role epigenetic modifications occurrence and progression elucidated. These not only affect gene expression but also impact critical biological behaviors cells, including proliferation, differentiation, apoptosis, invasion, metastasis. Notably, DNA methylation, an important regulatory mechanism, often manifests as global hypomethylation or hypermethylation specific promoter regions BC. Alterations this methylation pattern can lead to increased genomic instability, which profoundly influences proto-oncogenes suppressor genes. MiRNAs, noncoding small RNAs, participate various processes regulating target Consequently, work aims explore interaction mechanisms between miRNAs Research demonstrated that directly miRNA genes indirectly affects maturation functionality modulating status regions. Simultaneously, regulate levels targeting key enzymes such methyltransferases (DNMTs), thereby establishing feedback network. A deeper understanding crosstalk will contribute elucidating complexity dynamics disease, may provide new molecular targets strategies for early diagnosis, treatment, prognostic evaluation

Язык: Английский

Процитировано

0
Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis DOI Open Access
Shuanhu Li, Xin Zhou,

Qinchun Duan

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3252 - 3252

Опубликована: Апрель 1, 2025

Atherosclerosis, a chronic inflammatory disease characterized by lipid accumulation and immune cell infiltration, is linked to plaque formation cardiovascular events. While traditionally associated with metabolism endothelial dysfunction, recent research highlights the roles of autophagy clonal hematopoiesis (CH) in its pathogenesis. Autophagy, cellular process crucial for degrading damaged components, regulates macrophage homeostasis inflammation, both which are pivotal atherosclerosis. In macrophages, influences metabolism, cytokine regulation, oxidative stress, helping prevent instability. Defective exacerbates impairs cholesterol efflux, accelerates progression. Additionally, autophagic processes cells smooth muscle further contribute atherosclerotic pathology. Recent studies also emphasize interplay between CH, wherein somatic mutations genes like TET2, JAK2, DNMT3A drive expansion enhance responses plaques. These modify function, intensifying environment accelerating Chaperone-mediated (CMA), selective form autophagy, plays critical role regulating inflammation pro-inflammatory cytokines oxidized low-density lipoprotein (ox-LDL). Impaired CMA activity leads these substrates, activating NLRP3 inflammasome worsening inflammation. Preclinical suggest that pharmacologically may mitigate atherosclerosis animal models, reduced instability increases This review importance regulation focusing on formation, contributions CH. Building upon current advances, we propose hypothesis programmed death, intrinsic axis modulates fundamental functions playing complex development Understanding mechanisms offers potential therapeutic strategies targeting reduce burden disease.

Язык: Английский

Процитировано

0
Hypoxia-induced USP22 contributes to tumor stemness and chemoresistance in nasopharyngeal carcinoma via stabilizing HIF-1α DOI
Ke Chen,

S Li

Molecular & Cellular Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Язык: Английский

Процитировано

0
Single-cell profiling uncovers the intricate pathological niche diversity in brain, lymph node, bone, and adrenal metastases of lung cancer DOI Creative Commons
Le Liu, Yuan Zhou,

Zhenjun Ye

и другие.

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 10, 2025

Язык: Английский

Процитировано

0
Immune regulation: a new strategy for traditional Chinese medicine-based treatment of granulomatous lobular mastitis DOI Creative Commons

Yuan Lou,

Xu Han,

Zixuan Lu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 31, 2024

Granulomatous lobular mastitis (GLM) presents significant challenges, including high rates of morbidity, recurrence, and disability, ultimately impacting women's health quality life. Local autoimmune imbalance involving dysregulated cytokines immune cells has been recognized to play a key role in the pathology GLM. Traditional Chinese medicine (TCM), with its multi-component, multi-pathway multi-target characteristics, offers unique advantages broad prospects treatment Here, we review relationship between dysregulation GLM, as well regulatory mechanisms TCM-based interventions, aim providing new insights foundational knowledge for clinical while promoting further application development strategies

Язык: Английский

Процитировано

0
A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages DOI Creative Commons

Atsadang Boonmee,

Salisa Benjaskulluecha,

Patipark Kueanjinda

и другие.

Epigenetics & Chromatin, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 29, 2024

To avoid exaggerated inflammation, innate immune cells adapt to become hypo-responsive or "tolerance" in response successive exposure stimuli, which is a part of memory. Polycomb repressive complex 2 (PRC2) mediates the transcriptional repression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3) but little known about its role lipopolysaccharide (LPS)-induced tolerance macrophages. We examined unexplored roles EED, component PRC2, LPS tolerant In Eed KO macrophages, significant reduction H3K27me3 and increased active mark, H3K27ac, was observed. macrophages exhibited dampened pro-inflammatory cytokine productions (TNF-α IL-6) while increasing non-tolerizable genes upon tolerance. Pharmacological inhibition EED also reduced TNF-α IL-6 during Mechanistically, tolerized failed increase glycolytic activity. RNA-Seq analyses revealed that hallmarks hypoxia, TGF-β, Wnt/β-catenin signaling were enriched Among upregulated genes, promoter Runx3 found be associated with EED. Silencing partially rescued Enrichment decreased subset are indicating direct regulatory PRC2 on such genes. Motif enrichment analysis identified ETS family transcription factor binding sites absence Our results provided mechanistic insight into how via regulates epigenetically silencing play crucial as those TGF-β/Runx3 axis.

Язык: Английский

Процитировано

0