Mechanism of Action of Melatonin as a Potential Adjuvant Therapy in Inflammatory Bowel Disease and Colorectal Cancer

Nutrients, Journal Year: 2024, Volume and Issue: 16(8), P. 1236 - 1236

Published: April 21, 2024

Inflammatory bowel disease (IBD), a continuum of chronic inflammatory diseases, is tightly associated with immune system dysregulation and dysbiosis, leading to inflammation in the gastrointestinal tract (GIT) multiple extraintestinal manifestations. The pathogenesis IBD not completely elucidated. However, it an increased risk colorectal cancer (CRC), which one most common malignancies. In both CRC, complex interplay occurs between gut microbiota (GM), alteration GM composition. Melatonin, neuroendocrine hormone, was found be involved this interplay, especially since present high amounts gut, some protective effects. Actually, melatonin enhances integrity intestinal mucosal barrier, regulates response, alleviates inflammation, attenuates oxidative stress. Thereby, authors summarize multifactorial interaction focusing on new findings related mechanisms action addition its documented positive outcomes treatment these two pathologies possible future perspectives use as adjuvant therapy.

Language: Английский

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Unravelling the prognostic and operative role of intratumoural microbiota in non‐small cell lung cancer: Insights from 16S rRNA and RNA sequencing

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background Complex interrelationships between the microbiota and cancer have been identified by several studies. However, despite delineating microbial composition in non‐small cell lung (NSCLC), key pathogenic their underlying mechanisms remain unclear. Methods We performed 16S rRNA V3–V4 amplicon transcriptome sequencing on cancerous adjacent normal tissue samples from 30 patients with NSCLC, which clinical characteristics prognosis outcomes were collected. used to dissect perform correlations, conjunction sequencing, we determined potential underpinning significant actions. Results In comparing different sample types, more pronounced beta diversity disparity squamous carcinoma (LUSC) corresponding paired tissues. Concurrently, LUSC adenocarcinoma exhibited distinct traits at genus levels. Subsequently, four phyla, five classes, nine orders, 17 families 36 genera filtered out related outcomes. Intriguingly, a protective cluster was encompassing associated delayed disease recurrence, functional analyses suggested that these predominantly exerted metabolism‐related functions. Additionally, harmful (HMC) identified, including three genera. this HMC subsequent model analyses, intratumoural potentially implicated infection, inflammation immune regulation. Crucially, genus, Peptococcus , as an independent, detrimental NSCLC prognostic factor impacted via tumour necrosis (TNF) signalling. Conclusions substantial connection Protective primarily metabolic functions, whereas mainly modulation. Furthermore, may be adverse prognoses serve biomarker for patient management screening. Key points Four found prognosis. recurrence shorter survival earlier recurrence. impacting TNF

Language: Английский

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Investigating the Role of Quercetin, an Active Ingredient in Bazhen Decoction, in Targeting CXCL8 to Inhibit Macrophage M2 Polarization and Reshape the Immunological Microenvironment of Colorectal Cancer

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(1)

Published: Jan. 1, 2025

ABSTRACT Bazhen Decoction (Eight Treasures Decoction) has demonstrated efficacy in the treatment of colorectal cancer (CRC), yet active ingredients it and mechanisms underlying their anti‐cancer properties are not well understood. Through network pharmacology, effective components against CRC corresponding key genes were delineated. Molecular docking was executed to identify component targeting gene CXCL8, which led discovery Quercetin. The cellular thermal shift assay method then used verify binding interaction. cells treated with incremental concentrations Quercetin, cell viability evaluated by Cell Counting Kit‐8 calculate IC 50 , apoptosis rates determined flow cytometry. Expression apoptosis‐related proteins Bcl‐2 Cleaved caspase‐3 measured using western blot. impact Quercetin on macrophage polarization studied co‐culturing macrophages, assessing M1 M2 distribution via cytometry, quantifying cytokine levels (IL‐6, IL‐10, IL‐12, CXCL8) enzyme‐linked immunosorbent (ELISA). ingredient from exhibited a targeted affinity enabled inhibit proliferation induce apoptosis. overexpression CXCL8 associated promotion malignancy, presence could lessen cells. Moreover, leads diminished abundance macrophages an increase cytokines IL‐6 while reducing IL‐10 indicates that inhibitory effect polarization. is known for anti‐CRC effects, targets inhibits impede malignant behaviors macrophages. Thus, may be utilized as immunomodulatory agent treatment.

Language: Английский

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Uncovering the Effects and Molecular Mechanisms of Shaoyao Decoction Against Colorectal Cancer Using Network Pharmacology Analysis Coupled With Experimental Validation and Gut Microbiota Analysis

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(6)

Published: March 1, 2025

ABSTRACT Background Chronic gut inflammation and dysbiosis contribute significantly to colorectal cancer (CRC) development. Shaoyao decoction (SYD) is a well‐established Chinese medicine prescription. Besides ameliorating CRC via anti‐inflammatory effects, SYD modulates microbiota (GM) improve inflammatory responses in ulcerative colitis (UC). However, whether how suppresses by regulating GM remains largely unknown. Methods SD rats were orally administered for 7 days obtain medicated serum. We utilized liquid chromatography–mass spectrometry (LC–MS) analysis, GeneCards, DisGeNET, SwissTargetPrediction databases analyze blank SYD‐medicated rat serum, comparing the findings with those of aqueous extract previous studies identify circulating compounds/components predictable target genes. Using network pharmacology, potential active compounds corresponding hub genes associated modulating suppress selected molecular docking. In vivo experiments, transplantation tumor model was established BALB/c mice using CT26 cells, gavage 14 days. To investigate mechanism SYD‐regulated against CRC, HE IHC staining, Western blotting, 16S rRNA sequencing employed. Results LC–MS identified 26 computationally predicted Network pharmacology prioritized 13 targeting 8 inflammation/immunity‐related (IL‐17/TNF pathways), validated dose‐dependently suppressed growth ( p < 0.05, medium/high doses), as confirmed staining analysis Ki‐67. Notably, potentially delayed liver metastasis alleviated hepatic injury tumor‐bearing mice. blotting demonstrated SYD's inhibition IL‐17/TNF/NF‐κB axis, aligning computational predictions. revealed SYD‐enriched Akkermansia structural shifts, mechanistically linking remodeling anti‐tumor efficacy. Conclusions combats dual modulation signaling ecosystems (e.g., enrichment). This microbiota‐immune crosstalk positions adjunct conventional therapies, particularly patients dysbiosis.

Language: Английский

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The Gut-Wrenching Truth: Pathophysiology and Clinical Features of Intestinal Hyperpermeability Syndrome

European Journal of Medical and Health Research, Journal Year: 2025, Volume and Issue: 3(2), P. 147 - 154

Published: March 27, 2025

The microbes associated with the gut are called microbiota. There about 1000 species of bacteria weighing up to 1-2 kg in human gut. Microbial diversity increases age until it is stable. Humans have evolved live them and learned play their role body. Dysbiosis microbiota causes various ailments, disorders diseases humans. And all this due increased intestinal permeability caused by dysbiosis. present review discusses some pathophysiological clinical symptoms leaky syndrome, a highly controversial but logical relevant topic medical microbiology gastroenterology

Language: Английский

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