Flavonoids and their role in oxidative stress, inflammation, and human diseases DOI Creative Commons
Klaudia Jomová, Suliman Yousef Alomar,

Richard Valko

et al.

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111489 - 111489

Published: March 1, 2025

Oxidative stress and chronic inflammation are important drivers in the pathogenesis progression of many diseases, such as cancers breast, kidney, lung, others, autoimmune diseases (rheumatoid arthritis), cardiovascular (hypertension, atherosclerosis, arrhythmia), neurodegenerative (Alzheimer's disease, Parkinson's Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal (inflammatory bowel colorectal cancer), other disorders. With increasing demand for less toxic more tolerable therapies, flavonoids have potential to effectively modulate responsiveness conventional therapy radiotherapy. Flavonoids polyphenolic compounds found fruits, vegetables, grains, plant-derived beverages. Six twelve structurally different flavonoid subgroups dietary significance include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols epicatechin, epigallocatechin), flavonols quercetin, kaempferol), flavones luteolin, baicalein), flavanones hesperetin, naringenin), isoflavones (daidzein, genistein). The health benefits related their structural characteristics, number position hydroxyl groups presence C2=C3 double bonds, which predetermine ability chelate metal ions, terminate ROS radicals formed by Fenton reaction), interact with biological targets trigger a response. Based on these can exert both antioxidant or prooxidant properties, activity ROS-scavenging enzymes expression activation proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)), induce apoptosis autophagy, target key signaling pathways, nuclear factor erythroid 2-related 2 (Nrf2) Bcl-2 family proteins. This review aims briefly discuss mutually interconnected aspects oxidative inflammatory mechanisms, lipid peroxidation, protein oxidation, DNA damage, mechanism resolution inflammation. major part this article discusses role alleviating inflammation, two common components human diseases. results epidemiological studies also presented.

Language: Английский

Ulcerative colitis: molecular insights and intervention therapy DOI Creative Commons

Yuqing Liang,

Yang Li,

Chehao Lee

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Oct. 10, 2024

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis treatment of UC remain key areas research interest. Various factors, including genetic predisposition, immune dysregulation, alterations in the gut microbiota, are believed to contribute UC. Current treatments for include 5-aminosalicylic acids, corticosteroids, immunosuppressants, biologics. However, study reported that one-year clinical remission rate only around 40%. It necessary prompt exploration new modalities. Biologic therapies, such as anti-TNF-α monoclonal antibody JAK inhibitor, primarily consist small molecules targeting specific pathways, effectively inducing maintaining remission. Given significant role into intestinal microecologics, probiotics prebiotics, fecal microbiota transplantation (FMT) shows promising potential treatment. Additionally, medicinal herbs, chili pepper turmeric, used complementary therapy have shown results management. This article reviews recent findings on mechanisms UC, susceptibility, cell dynamics cytokine regulation, alterations. also discusses current applications biologic therapy, herbal FMT, along with their prospects challenges.

Language: Английский

Citations

8
Tandem kinase proteins across the plant kingdom DOI
Tamara Reveguk, Andrii Fatiukha,

Evgenii Potapenko

et al.

Nature Genetics, Journal Year: 2025, Volume and Issue: 57(1), P. 254 - 262

Published: Jan. 1, 2025

Language: Английский

Citations

1
Effects of hypoxia on the heart of the juvenile four-finger threadfin (Eleutheronema tetradactylum) based on physiological indicators and transcriptome analysis DOI Creative Commons
Yi Lu, Eric Amenyogbe, Ye Yang

et al.

Frontiers in Marine Science, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 5, 2025

This study evaluated the effects of hypoxia on heart juvenile four-finger threadfin ( Eleutheronema tetradactylum ) through physiological and transcriptome analysis. Juveniles with an average weight 122.82 g length 24.60 cm were used. Hypoxia significantly increased serum myocardial enzyme activities, including creatine kinase (CK), kinase-MB isoenzyme, lactate dehydrogenase (LDH), α-hydroxybutyrate (HDBH). These indicators initially rose then declined, reflecting cardiac stress suggesting their potential as early biomarkers for real-time aquaculture monitoring. Histological analysis revealed structural damage in fibers under hypoxia, increasing severity over time. underscores need to minimize oxygen fluctuations prevent tissue degeneration. Transcriptome identified upregulated genes involved cell communication, immune responses, intracellular signaling, offering targets breeding hypoxia-tolerant species. Kyoto Encyclopedia Genes Genomes pathway enrichment highlighted key pathways such mitogen-activated protein (MAPK), hypoxia-inducible factor-1 (HIF-1), endocytosis, phagosome formation. The MAPK plays a critical role cellular survival, proliferation, apoptosis. Hypoxia-induced activation MAPKs like ERK, JNK, p38 regulates stress-responsive genes. HIF-1 signaling homeostasis, HIF-1α stabilizing hypoxia-responsive VEGFA, which promotes vascular remodeling enhances delivery. findings collectively offer practical applications enhancing management, monitoring biochemical markers, adopting breeding, adjusting environmental conditions mitigate stress, ensuring better productivity sustainability. research provides foundation further studies molecular mechanisms

Language: Английский

Citations

1
Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know? DOI Creative Commons
Carmela Rita Balistreri, Roberto Monastero

Brain Sciences, Journal Year: 2023, Volume and Issue: 14(1), P. 19 - 19

Published: Dec. 23, 2023

The term “neuroinflammation” defines the typical inflammatory response of brain closely related to onset many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through efforts research. Consequently, new cellular molecular mechanisms, diverse conventional, emerging. In listing some those that will be subject our description discussion, essential important roles peripheral infiltrated monocytes clonotypic cells, alterations in gut–brain axis, dysregulation apelinergic system, endothelial glycocalyx component neuronal vascular units, variations expression genes levels encoding molecules by action microRNAs (miRNAs), or other epigenetic factors distinctive transcriptional factors, as role autophagy, ferroptosis, sex differences, modifications circadian cycle. Such can add significantly understanding complex etiological puzzle neuroinflammation ND. addition, they could represent biomarkers targets ND, which increasing elderly.

Language: Английский

Citations

19
Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation DOI Open Access
Weiyuan Wang,

Melanie Cristina Lopez McDonald,

Rajashree Hariprasad

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1387 - 1387

Published: March 31, 2024

Despite advances in our understanding of molecular aspects oncogenesis, cancer remains a leading cause death. The malignant behavior cell is driven by the inappropriate activation transcription factors. In particular, signal transducers and activators (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, differentiation, are frequently activated inappropriately wide spectrum human cancers. Multiple signaling pathways converge on STATs, highlighting their importance development progression oncogenic diseases. STAT3 STAT5 two members STAT protein family that most cancers can drive pathogenesis directly. inhibitors targeting has been subject intense investigations last decade, although effective treatment options remain limited. this review, we investigate specific roles normal physiology biology, discuss opportunities challenges pharmacologically proteins upstream activators, offer insights into novel therapeutic strategies to identify therapeutics.

Language: Английский

Citations

7
Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement DOI Open Access
Evgeni Gusev, Alexey Sarapultsev

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6389 - 6389

Published: June 9, 2024

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase COVID-19. Characterized by myriad symptoms across different organ systems, LC presents significant diagnostic management challenges. Central disorder is role low-grade inflammation, non-classical inflammatory response that contributes chronicity diversity observed. This review explores pathophysiological underpinnings LC, emphasizing importance inflammation core component. By delineating pathogenetic relationships clinical manifestations this article highlights necessity for an integrated approach employs both personalized medicine standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding but inform development therapeutic strategies could be applicable chronic conditions with similar features.

Language: Английский

Citations

7
JAK Inhibitors in Rheumatoid Arthritis: Immunomodulatory Properties and Clinical Efficacy DOI Open Access
Kajetan Kiełbowski,

Paulina Plewa,

Aleksandra Wiktoria Bratborska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8327 - 8327

Published: July 30, 2024

Rheumatoid arthritis (RA) is a highly prevalent autoimmune disorder. The pathogenesis of the disease complex and involves various cellular populations, including fibroblast-like synoviocytes, macrophages, T cells, among others. Identification signalling pathways molecules that actively contribute to development crucial understanding mechanisms involved in chronic inflammatory environment present affected joints. Recent studies have demonstrated Janus kinase/signal transducer activator transcription (JAK/STAT) pathway regulates behaviour immune cells contributes progression RA. Several JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, filgocitinib, been developed, their efficacy safety patients with RA comprehensively investigated number clinical trials. Consequently, inhibitors approved registered treatment for In this review, we discuss involvement JAK/STAT summarise potential beneficial effects implicated disease. Moreover, most important phase 3 trials evaluated use these agents patients.

Language: Английский

Citations

7
TLR4/TNFR1 blockade suppresses STAT1/STAT3 expression and increases SOCS3 expression in modulation of LPS-induced macrophage responses DOI Creative Commons

Ritasha Sawoo,

Biswadev Bishayi

Immunobiology, Journal Year: 2024, Volume and Issue: 229(5), P. 152840 - 152840

Published: Aug. 3, 2024

Due to the urgent need create appropriate treatment techniques, which are currently unavailable, LPS-induced sepsis has become a serious concern on global scale. The primary active component in pathophysiology of inflammatory diseases such as is Gram-negative bacterial lipopolysaccharide (LPS). LPS interacts with cell surface TLR4 macrophages, causing formation reactive oxygen species (ROS), TNF-α, IL-1β and oxidative stress. It also significantly activates MAPKs NF-κB pathway. Excessive production pro-inflammatory cytokines one characteristic features onset progression inflammation. Cytokines mainly signal through JAK/STAT We hypothesize that blocking along TNFR1 might be beneficial suppressing effects STAT1/STAT3 due stimulation SOCS3 proteins. Prior challenge, macrophages were treated antibodies against either individually or combination. On analysis macrophage populations by flowcytometry, it was seen receptor blockade facilitated phenotypic shift M1 towards M2 resulting lowered Blocking TLR4/TNFR1 upregulated mTOR expressions enabled transition anti-inflammatory phenotype, crucial curbing responses. Also reduction IL-6, activation STAT1 STAT3 molecules observed our combination group. All these results indicated neutralization both provide new insights establishing an alternative therapeutic strategy for LPS-sepsis.

Language: Английский

Citations

6
DL-3-n-Butylphthalide Ameliorates Post-stroke Emotional Disorders by Suppressing Neuroinflammation and PANoptosis DOI

Yanhui Cui,

Zhaolan Hu,

Laifa Wang

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(8), P. 2215 - 2227

Published: June 4, 2024

Language: Английский

Citations

5
Common cytokine receptor gamma chain family cytokines activate MAPK, PI3K, and JAK/STAT pathways in microglia to influence Alzheimer’s Disease DOI Creative Commons

Hannah Zuppe,

Erin G. Reed-Geaghan

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Sept. 11, 2024

Dementia is an umbrella term used to describe deterioration of cognitive function. It the seventh leading cause death and one major causes dependence among older people globally. Alzheimer's Disease (AD) contributes approximately 60-70% dementia cases characterized by accumulation amyloid plaques tau tangles in brain. Neuroinflammation now widely accepted as another disease hallmark, playing a role both response perpetuation processes. Microglia are brain-resident immune cells that initially effective at clearing but contribute damaging inflammatory milieu brain progresses. Circulating peripheral this environment through cytokine secretion, creating positive feedback loop with microglia. One group these peripherally derived cytokines acting on microglia common receptor γ chain family. These bind heterodimer receptors activate three signaling pathways: MAPK, PI3K, JAK/STAT. This perspective will look mechanisms pathways highlight future directions research potential therapeutics.

Language: Английский

Citations

5