NF‐κB signaling in inflammation and cancer

MedComm, Год журнала: 2021, Номер 2(4), С. 618 - 653

Опубликована: Дек. 1, 2021

Abstract Since nuclear factor of κ‐light chain enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism NF‐κB for 35 years, which lead significant progress. Meanwhile, molecular mechanisms activation also illuminated, cascades signaling events leading activity key components pathway are identified. It has suggested plays an important role human diseases, especially inflammation‐related diseases. These studies make attractive target disease treatment. This review aims summarize knowledge family members NF‐κB, as well basic activation. We will effects dysregulated on inflammation, tumorigenesis, tumor microenvironment. The progression translational study drug development targeting inflammatory diseases cancer treatment potential obstacles be discussed. Further investigations precise functions physiological pathological settings underlying urgent need develop drugs treatment, with minimal side effects.

Язык: Английский

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Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations

Frontiers in Aging, Год журнала: 2022, Номер 3

Опубликована: Июль 12, 2022

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These have shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of opposite effects, extending lifespan. In humans, levels decline with age, chronic kidney diabetes, Alzheimer's disease other conditions. Low correlate an increase the death rate from all causes. acts either obligate coreceptor fibroblast growth factor 23 (FGF23), or soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced kidneys, but also brain, pancreas tissues. On tubular-cell membranes, it associates FGF receptors to bind FGF23. Produced bones, FGF23 regulates excretion phosphate (phosphaturic effect) vitamin D metabolism. Lack results hyperphosphatemia hypervitaminosis D. With human function often deteriorates, lowering levels. This appears promote age-related pathology. Remarkably, inhibits four pathways that been linked aging various ways: Transforming β (TGF-β), insulin-like 1 (IGF-1), Wnt NF-κB. can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis neoplasia. Furthermore, increases cell-protective antioxidant enzymes through Nrf2 FoxO. accord, preclinical therapy ameliorated renal, cardiovascular, diabetes-related neurodegenerative diseases, well cancer. s-Klotho injection was effective, requires further investigation. Several drugs enhance circulating levels, some cross blood-brain barrier potentially act brain. clinical trials, increased noted renin-angiotensin system inhibitors (losartan, valsartan), statin (fluvastatin), mTOR (rapamycin, everolimus), pentoxifylline. work, antidiabetic (metformin, GLP-1-based, GABA, PPAR-γ agonists) enhanced Klotho. traditional medicines and/or nutraceuticals rodents, including astaxanthin, curcumin, ginseng, ligustilide resveratrol. Notably, exercise sport activity review addresses molecular, physiological therapeutic aspects

Язык: Английский

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The role of NF-κB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 163, С. 114822 - 114822

Опубликована: Май 3, 2023

Breast cancer (BC) is the second most fatal disease and prime cause of allied female deaths. BC caused by aberrant tumor suppressor genes oncogenes regulated transcription factors (TFs) like NF-κB. NF-κB a pro-inflammatory TF that crucially alters expressions various associated with inflammation, cell progression, metastasis, apoptosis modulates network underlie tumorigenesis. Herein, we focus on signaling pathways, its regulators, rationale for targeting This review also includes TFs maintain crosstalk their roles in promoting angiogenesis metastasis. In addition, discuss importance combination therapies, resistance to treatment, potential novel therapeutic strategies including nanomedicine targets

Язык: Английский

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Polyphenols as Antioxidant/Pro-Oxidant Compounds and Donors of Reducing Species: Relationship with Human Antioxidant Metabolism

Processes, Год журнала: 2023, Номер 11(9), С. 2771 - 2771

Опубликована: Сен. 16, 2023

In this review, we have focused mainly on the study of their antioxidant and pro-oxidant capacity, analysis oxidation catechol group to o-quinone. The redox balance established between different oxidase reductase enzymes generates reducing species, H+ e−, allows polyphenolic groups quinones be reversible. This continuous these nucleophilic electrophilic substances activation NRF2/ARE axis, which regulates cellular responses against oxidative stress, as well cell proliferation. Understanding ambivalent character polyphenols, can act simultaneously antioxidants pro-oxidants, will allow design specific therapies that serve science medicine in tasks.

Язык: Английский

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Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 8, 2024

The increasing life expectancy has led to a higher incidence of age-related neurodegenerative conditions. Within this framework, neuroinflammation emerges as significant contributing factor. It involves the activation microglia and astrocytes, leading release pro-inflammatory cytokines chemokines infiltration peripheral leukocytes into central nervous system (CNS). These instances result in neuronal damage neurodegeneration through activated nucleotide-binding domain leucine-rich repeat containing (NLR) family pyrin protein 3 (NLRP3) nuclear factor kappa B (NF-kB) pathways decreased erythroid 2-related 2 (Nrf2) activity. Due limited effectiveness regarding inhibition neuroinflammatory targets using conventional drugs, there is challenging growth search for innovative therapies alleviating CNS diseases or even before their onset. Our results indicate that interventions focusing on Interleukin-Driven Immunomodulation, Chemokine (CXC) Receptor Signaling Expression, Cold Exposure, Fibrin-Targeted strategies significantly promise mitigate processes. approaches demonstrate potential anti-neuroinflammatory effects, addressing conditions such Multiple Sclerosis, Experimental autoimmune encephalomyelitis, Parkinson’s Disease, Alzheimer’s Disease. While findings are promising, immunomodulatory often face limitations due Immune-Related Adverse Events. Therefore, conduction randomized clinical trials matter mandatory, will pave way promising future development new medicines with specific therapeutic targets.

Язык: Английский

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Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 15, 2024

Abstract Cancer is a major public health problem worldwide with more than an estimated 19.3 million new cases in 2020. The occurrence rises dramatically age, and the overall risk accumulation combined tendency for cellular repair mechanisms to be less effective older individuals. Conventional cancer treatments, such as radiotherapy, surgery, chemotherapy, have been used decades combat cancer. However, emergence of novel fields research has led exploration innovative treatment approaches focused on immunotherapy, epigenetic therapy, targeted multi-omics, also multi-target therapy. hypothesis was based that drugs designed act against individual targets cannot usually battle multigenic diseases like Multi-target therapies, either combination or sequential order, recommended acquired intrinsic resistance anti-cancer treatments. Several studies multi-targeting treatments due their advantages include; overcoming clonal heterogeneity, lower multi-drug (MDR), decreased drug toxicity, thereby side effects. In this study, we'll discuss about drugs, benefits improving recent advances field multi-targeted drugs. Also, we will study performed clinical trials using therapeutic agents treatment.

Язык: Английский

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Histone lactylation inhibits RARγ expression in macrophages to promote colorectal tumorigenesis through activation of TRAF6-IL-6-STAT3 signaling

Cell Reports, Год журнала: 2024, Номер 43(2), С. 113688 - 113688

Опубликована: Янв. 21, 2024

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype manipulate them for therapeutic purposes remain be explored. Here, we show that TME, RARγ is downregulated macrophages, its expression correlates poor prognosis patients colorectal cancer (CRC). In interacts necrosis factor receptor-associated 6 (TRAF6), which prevents TRAF6 oligomerization autoubiquitination, leading inhibition of nuclear κB signaling. tumor-derived lactate fuels H3K18 lactylation prohibit gene transcription consequently enhancing interleukin-6 (IL-6) levels TME endowing tumor-promoting functions via activation signal transducer activator 3 (STAT3) signaling CRC cells. We identified nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding inhibit TRAF6-IL-6-STAT3 This study unravels lactate-driven macrophage function remodeling highlights NDGA as candidate compound treating CRC.

Язык: Английский

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The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis

Chemico-Biological Interactions, Год журнала: 2024, Номер 394, С. 111002 - 111002

Опубликована: Апрель 9, 2024

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates morbidity death across many demographic groups. An industrial chemical common environmental contaminant, formaldehyde (FA) presents serious concerns to the respiratory system, including onset aggravation lung disorders. Epidemiological studies have shown significant associations between FA exposure levels incidence severity several diseases. causes inflammation in tract via immunological activation, oxidative stress, airway remodelling, aggravating pre-existing pulmonary compromising function. Additionally, functions as sensitizer, causing allergic responses hypersensitivity pneumonitis sensitive people. Understanding complicated processes behind formaldehyde-induced is critical for directing targeted strategies aimed at minimizing exposures alleviating burden formaldehyde-related illnesses on health. This abstract explores intricate relationship diseases, asthma, bronchitis, inflammation, injury fibrosis.

Язык: Английский

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Anti- and pro-oxidant properties of polyphenols and their role in modulating glutathione synthesis, activity and cellular redox potential: Potential synergies for disease management

Advances in Redox Research, Год журнала: 2024, Номер 11, С. 100099 - 100099

Опубликована: Апрель 9, 2024

Cellular metabolic activities are controlled by pathways catalyzed enzymes, closely regulated signal transduction through induction or inhibition processes. Metabolic disorders and cellular dysregulation often linked to redox-dependent signaling in a complex relationship. Glutathione (GSH) polyphenols which known regulators of redox homeostasis have been studied immensely. However, no study has considered their potential interactions synergies as novel mechanisms control disorders. GSH does not only act an antioxidant, but ligand that binds inactivate enzymes toxins. Also, depending on environment, structure, pH, concentration availability transition metals high charge density, may possess either anti-oxidant pro-oxidant properties. Owing remarkable influence individual compounds, this the between disease management. Generally, both reduce oxidative stress normal cells under exacerbating conditions low GSH/GSSG ratio, induce apoptotic abnormal cells. Investigating effects polyphenol concentrations, metals, caloric restriction structure apoptosis proliferation cancer future be basis for synergistic exploitation

Язык: Английский

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Role of the Extracellular Matrix in Cancer: Insights into Tumor Progression and Therapy

Advanced Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Abstract The extracellular matrix (ECM) serves not only as a structural scaffold but also an active regulator of cancer progression, profoundly influencing tumor behaviour and the microenvironment (TME). This review focuses into pivotal role ECM alterations in facilitating metastasis explores therapeutic strategies aimed at counteracting these changes. We analyse targeted interventions against collagen, including approaches to inhibit its biosynthesis disrupt associated signalling pathways critical for architecture cell migration. Additionally, therapies addressing hyaluronan are reviewed, highlighting methods suppress synthesis enzymatic degrade it, thereby mitigating tumor‐promoting effects. discussion extends innovative modulating stiffness, focusing on roles cancer‐associated fibroblasts lysyl oxidases, which key contributors remodelling mechanical signalling. By strategically modifying components, aim enhance efficacy existing treatments, tackle resistance mechanisms, achieve more durable outcomes. Insights from recent studies clinical trials highlight promise overcoming treatment improving patient Advancing our understanding biology leads development effective therapies.

Язык: Английский

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