Versatile function of NF-ĸB in inflammation and cancer

Experimental Hematology and Oncology, Journal Year: 2024, Volume and Issue: 13(1)

Published: July 16, 2024

Abstract Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, stemness. The function of NF-ĸB cancer progression response to chemotherapy has gained increasing attention. This review highlights the inflammation control, biological mechanisms, therapeutic implications treatment. is instrumental altering release inflammatory factors TNF-α, IL-6, IL-1β, which are key regulation carcinogenesis. Specifically, conditions including colitis, upregulation can intensify inflammation, potentially leading development colorectal cancer. Its pivotal extends regulating tumor microenvironment, impacting components macrophages, fibroblasts, T cells, natural killer cells. influences tumorigenesis dampen anti-tumor responses. Additionally, modulates death notably by inhibiting apoptosis ferroptosis. It also dual stimulating or suppressing autophagy cancers. Beyond these functions, controlling stem fostering angiogenesis, metastatic potential through EMT induction, reducing sensitivity radiotherapy. Given its oncogenic capabilities, research focused on products small molecule compounds that suppress NF-ĸB, offering promising avenues for therapy.

Language: Английский

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Silymarin and Inflammation: Food for Thoughts

Antioxidants, Journal Year: 2024, Volume and Issue: 13(1), P. 98 - 98

Published: Jan. 14, 2024

Inflammation is a vital defense mechanism, creating hostile conditions for pathogens, preventing the spread of tissue infection and repairing damaged tissues in humans animals. However, when inflammation resolution delayed or compromised as result its misregulation, process proceeds from acute phase to chronic inflammation, leading development various illnesses. It proven that redox balance disturbances oxidative stress are among major factors inducing NF-κB over-inflammation. Therefore, anti-inflammatory properties natural antioxidants have been widely tested vitro vivo systems. Accumulating evidence indicates silymarin (SM) main constituent silibinin/silybin (SB) great potential an anti-inflammation agent. The mechanism SM/SB action attributed inhibition TLR4/NF-κB-mediated signaling pathways downregulated expression pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, IL-12, IL-23, CCL4, CXCL10, etc. Of note, same model systems, was able upregulate cytokines (IL-4, IL-10, IL-13, TGF-β, etc.) lipid mediators involved inflammation. inflammatory were clearly demonstrated systems based on immune (macrophages monocytes) non-immune (epithelial, skin, bone, connective cancer) cells. At time, confirmed number models, toxicity nonalcoholic fatty liver disease, ischemia/reperfusion stress-induced injuries, ageing exercising wound healing many other relevant seems likely activities key elements health-promoting these phytochemicals.

Language: Английский

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Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: March 31, 2025

Language: Английский

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Synthesis, characterization, enzyme inhibition, antioxidant, anticancer and antimicrobial potential of organotin(IV) derivatives of 4-fluorophenoxyacetic acid

Arabian Journal of Chemistry, Journal Year: 2024, Volume and Issue: 17(4), P. 105698 - 105698

Published: Feb. 28, 2024

Five organotin(IV) derivatives (1–5) of general formula R3SnL and R2SnL2, where R = C4H9 {1, 3}, CH3 {2 4}, C6H5 {5} L represents 4-fluorophenoxyacetate ligand were synthesized by the condensation reaction corresponding chloride sodium-4-fluorophenoxyaceate salt in dry chloroform under reflux condition. The elemental analysis has confirmed expected composition complexes. Δν values (less than 200 cm−1) calculated from FT-IR spectra revealed bridging/chelating bidentate coordination carboxylate to tin. single crystal XRD shown polymeric chain structures for complexes 1 2 with bridging connecting tin atoms having trigonal bipyramidal geometry. In complex 3, atom chelating anisobidentate ligands adopted a highly distorted octahedral Quantum chemical studies have good correlation between experimental theoretically geometric parameters. Hirshfeld surface fingerprint plots calculations H…H interactions as major intermolecular contacts present within 1–3. simulated (1H 13C) NMR found be agreement. vitro enzyme inhibition {acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase B (MAO-B), alpha-glucosidase, dipeptidyl peptidase-4, cyclooxygenase (COX) lipoxygenase (LOX)}, antioxidant [DPPH 2,2-diphenyl-1-picrylhydrazyl ABTS 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid] antileishmanial assays dose dependent responses test compounds. Complexes higher activities compared free acid. particularly more active acetylcholinesterase (BChE) inhibitors, especially 3 (IC50 0.60 µg/mL) was even potent standard drug Galantamine 2.82 µg/mL). MTT [MTT= (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide tetrazolium)] assay showed anticancer activity 4 12.54 ± 0.19 µg/mL), 5 16.44 0.17 4-fluorophenoxyacetic acid (HL) 21.95 0.09 among tested compounds towards brain cancer cell line (Malignant glioma U87). nonmalignant human embryonic kidney HEK293 cells less vulnerable antimicrobial assays, Cefixime against C. albicans P. aeruginosa, respectively.

Language: Английский

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Novel insights into rosacea's role in cancer risk: A Mendelian randomization approach

Skin Research and Technology, Journal Year: 2024, Volume and Issue: 30(5)

Published: May 1, 2024

Abstract Background Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long‐term inflammatory skin condition and had reported link with increased risk for several types of malignancies, but evidence causality lacking. Objectives To systematically estimate the causal relationship between rosacea cancer, including cutaneous malignant melanoma (CMM), squamous cell carcinoma (cSCC), basal (BCC), actinic keratosis (AK), thyroid breast glioma hepatic as well explore potential underlying pathogenesis. Methods We conducted bidirectional two‐sample Mendelian randomization study probe relationships cancer. Instrumental variables were established using genome‐wide significant single nucleotide polymorphisms associated cancers. The assessment was carried out through multiple methods, robustness results evaluated via sensitivity analyses. Results There no indication effects on CMM ( p ivw = 0.71), cSCC 0.45), BCC 0.90), AK 0.73), 0.59), 0.15), 0.07), genetic an susceptibility human epidermal growth factor receptor (HER)‐negative neoplasm (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02–1.18; 0.01). TANK (TRAF family member nuclear kappa B (NFKB) activator) identified common protective gene both (OR, 0.90; CI, 0.82–0.99; 0.048) HER‐negative 0.86; 0.75–0.98; 0.032), which primarily enriched in negative regulation NF‐κB signal transduction may contribute links this subtype Conclusions Our findings provide suggestive risk.

Language: Английский

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Advances in targeting tumor microenvironment for immunotherapy

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

Published: Oct. 3, 2024

The tumor microenvironment (TME) provides essential conditions for the occurrence, invasion, and spread of cancer cells. Initial research has uncovered immunosuppressive properties TME, which include low oxygen levels (hypoxia), acidic (low pH), increased interstitial pressure, heightened permeability vasculature, an inflammatory microenvironment. presence various components leads to immune evasion affects immunotherapy efficacy. This indicates potential value targeting TME in immunotherapy. Therefore, remodeling become effective method enhancing host responses against tumors. In this study, we elaborate on characteristics composition how it weakens surveillance summarize targeted therapeutic strategies regulating TME.

Language: Английский

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Precision Meets Repurposing: Innovative Approaches in Human Papillomavirus and Epstein-Barr Virus-Driven Cancer Therapy

Cancer Letters, Journal Year: 2024, Volume and Issue: 607, P. 217318 - 217318

Published: Nov. 8, 2024

Language: Английский

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Flavonoids and Other Polyphenols: Bioactive Molecules from Traditional Medicine Recipes/Medicinal Plants and Their Potential for Phytopharmaceutical and Medical Application

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5760 - 5760

Published: Dec. 5, 2024

Currently, natural bioactive ingredients and/or raw materials are of significant interest to scientists around the world. Flavonoids and other polyphenols a major group phytochemicals that have been researched noted as molecules. They offer several pharmacological medical benefits. This current review aims (1) illustrate their benefits for human health, such antioxidant, anti-aging, anti-cancer, anti-inflammatory, anti-microbial, cardioprotective, neuroprotective, UV-protective effects, also (2) perform quality evaluation traditional medicines future application. Consequently, keywords were searched on Scopus, Google Scholar, PubMed so search related publications. Then, those publications carefully checked in order find non-redundant studies matched objective this review. According review, researchers worldwide very interested discovering potential flavonoids polyphenols, used taken from medicinal plants, relation pharmaceutical applications. Many focus health tested using silico, vitro, vivo models. However, few carried out clinical trials trustworthy subject sizes accordance with practice guidelines. Additionally, interesting research directions perspectives highlighted work.

Language: Английский

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Organotin(IV) derivatives of 4-chloro-2-methylphenoxyacetic acid: synthesis, spectral characterization, X-ray structures, anticancer, enzyme inhibition, antileishmanial, antimicrobial and antioxidant activities

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Jan. 3, 2025

Four organotin(IV) carboxylate complexes; (C4H9)3SnL (1), CH3SnL (2), (C4H9)2SnL2 (3) and (CH3)2SnL2 (4) are synthesized by the condensation reaction of chlorides with sodium-4-chloro-2-methylphenoxyacetate (NaL). The FT-IR spectra suggested bridging/chelating bidentate coordination ligand to tin atom. Single-crystal XRD analysis authenticated findings for 1 2. NMR study has shown no significant differences in signals free coordinated except absence a proton up-filed/down-field shift C signal carboxyl group spectra. Complexes 1–4 have better enzyme inhibition, antioxidant, antimicrobial, anticancer activities compared acid. Complex 3 was most active inhibitor AChE, BChE, α-glucosidase α-amylase IC50 values 43.76, 102.39, 232.71 91.84 µg/mL, respectively. Additionally, 7.52 8.77 µg/mL DPPH ABTS assays, respectively antioxidant than standard. 4 efficient MAO-B COX-2 enzymes 106.99 12.98 respectively, while (IC50 = 38.97 µg/mL) highest 5-LOX inhibition potential. range 237.51–168.35 antileishmanial activity HL 277.57 µg/mL). compounds showed good potent antiproliferative malignant glioma U87 cells 12.54 ± 0.05 37.65 0.04 µg/mL. Antimicrobial promising results standards some cases.

Language: Английский

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Epigenetic age acceleration and methylation differences in IgG4-related cholangitis and primary sclerosing cholangitis

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 16, 2025

Abstract Background IgG4-related cholangitis (IgG4-SC) and primary sclerosing (PSC) are chronic fibro-inflammatory hepatobiliary conditions, with genetic, environmental, immunologic risk factors, in which epigenetic alterations may provide insights into pathophysiology novel biomarkers. This study is the first to assess methylation signatures IgG4-SC. Results Whole blood DNA profiling genotyping was performed 264 individuals; 47 IgG4-SC, 65 PSC, 64 ulcerative colitis (UC), 88 healthy controls. We identified 19 significant differences between IgG4-SC controls 38 PSC shared 8 probes. Inflammatory genes (including CEP97 , IFNAR1 TXK HERC6 C5orf36 PYY MTRNR2L1 ) were predominantly involved dysregulated methylation. Epigenetic age acceleration observed patients but not those or UC. meQTL analyses identify genetic determinants of revealed a strong human leucocyte antigen (HLA) signal both ( HLA-DQB2 HLA-DPA1 HLA-F HLA-DRA ). Conclusions biological providing disease pathogenesis, highlight role variation especially within HLA region shaping methylome.

Language: Английский

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