Effect of zearalenone on the jejunum of weaned gilts through the Epac1/Rap1/JNK pathway DOI
Heng Liu, Lulu Ma,

Jiawei Fu

и другие.

Journal of Animal Science, Год журнала: 2024, Номер 102

Опубликована: Янв. 1, 2024

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin produced by Fusarium strains that harmful to the intestinal health of animals and widely present in contaminated crops. The objective this study was investigate potential therapeutic target ZEN-induced jejunal damage weaned gilts. Sixteen gilts either received basal diet or supplemented with 3.0 mg/kg ZEN 32-d experiment. results showed at concentration activated inflammatory response caused oxidative stress (P < 0.05). exposure resulted upregulation 0.05) Exchange protein directly cAMP 1/Ras-related protein1/c-Jun N-terminal kinase (Epac1/Rap1/JNK) signaling pathway jejunum vivo porcine epithelial cells vitro. cell viability, EdU-positive cells, mRNA expression B-cell lymphoma-2 (Bcl-2) were decreased, whereas reactive oxygen species production expressions Bcl-2-associated X (Bax) Cysteine-aspartic acid protease 3 (Caspase3) increased ZEN. However, Bcl-2 decreased Bax caspase3 after Epac1 blocked. These collectively indicated mg /kg induced via Epac1/Rap1/JNK pathway.

Язык: Английский

Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets DOI Creative Commons
Yecan Pan,

Zishu Li,

Xiaoyu Zhao

и другие.

Foods, Год журнала: 2024, Номер 13(4), С. 612 - 612

Опубликована: Фев. 18, 2024

Ginger has been reported to potentially treat Alzheimer’s disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In study, a combination of network pharmacology, molecular docking, dynamic simulation technology was used screen active substances that regulate AD explore mechanisms. The TCMSP, GeneCards, OMIM, DisGeNET databases were utilized obtain 95 cross-targets related ginger’s ingredients as key targets. A functional enrichment analysis revealed pathways in which may be involved regulating include response exogenous stimuli, oxidative stress, toxic substances, lipid metabolism, among others. Furthermore, drug-active ingredient–key target interaction diagram constructed, highlighting 6-Gingerol is associated with 16 Additionally, protein–protein (PPI) mapped targets, HUB genes (ALB, ACTB, GAPDH, CASP3, CAT) identified. Based on results pharmacology cell experiments, selected ingredient further investigation. Molecular docking performed between its top three proteins strongest binding affinities (ACHE, MMP2, PTGS2) chosen dynamics together CASP3 protein gene. findings indicate exhibits strong ability these suggesting potential role at level, well abnormal cholinesterase metabolism apoptosis, other regulatory pathways. These provide solid theoretical foundation future vitro experiments using actual cells animal investigate application 6-Gingerol.

Язык: Английский

Процитировано

4
Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPARγ-PGC1α-FNDC5 Pathways DOI Creative Commons

Avital Horwitz,

Ruth Birk

Biomolecules, Год журнала: 2024, Номер 14(6), С. 643 - 643

Опубликована: Май 30, 2024

Acute pancreatitis (AP) entails pancreatic inflammation, tissue damage and dysregulated enzyme secretion, including lipase (PL). The role of irisin, an anti-inflammatory anti-apoptotic cytokine, in AP exocrine stress is unclear. We have previously shown that irisin regulates PL through the PPARγ-PGC1α-FNDC5 pathway. In this study, we investigated irisin's pathway on vitro (AR42J-B13) ex vivo (rat primary acinar) models using molecular, biochemical immunohistochemistry methodology. Pancreatitis induction (cerulein (cer)) resulted a significant up-regulation axis, expression secretion endoplasmic reticulum (ER) unfolded protein response (UPR) signal-transduction markers (CHOP, XBP-1 ATF6). Irisin addition cer-pancreatitis state down-regulation PPARγ nucleus-translocation inflammatory (TNFα IL-6) parallel to diminished (in models). up-regulated pro-survival UPR (ATF6 XBP-1) reduced pro-apoptotic (CHOP) under induced ER (tunicamycin), consequently increasing cells viability. Irisin's effect was abolished inhibition. Our findings suggest as potential therapeutic option for via its ability up-regulate signals activate

Язык: Английский

Процитировано

4
The Application Potential of the Regulation of Tregs Function by Irisin in the Prevention and Treatment of Immune-Related Diseases DOI Creative Commons
Zhengjiang Wang, Jiaqi Xu,

Liqun Mo

и другие.

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 3005 - 3023

Опубликована: Июль 1, 2024

Abstract: Irisin is a muscle factor induced by exercise, generated through the proteolytic cleavage of membrane protein fibronectin type III domain-containing 5 (FNDC-5). Numerous studies have shown that irisin plays significant role in regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing systemic inflammatory responses, providing neuroprotection. Additionally, can exert immunomodulatory functions regulatory T cells (Tregs). Tregs are highly differentiated subset mature play key maintaining self-immune homeostasis closely related to infections, inflammation, immune-related diseases, tumors. exerts persistent positive effects on Treg cell various mechanisms, including differentiation proliferation, improving their function, modulating balance immune cells, increasing production anti-inflammatory cytokines, enhancing metabolic functions, thereby helping maintain prevent diseases. As an important myokine, interacts with receptors membrane, activating multiple intracellular signaling pathways regulate function. Although specific receptor for has not been fully identified, integrins considered potential receptors. activates pathways, AMPK, MAPK, PI3K/Akt, integrin receptors, exerting biological effects. These research findings provide clues understanding mechanisms irisin's action theoretical basis its applications diseases immunomodulation. This article reviews relationship between Tregs, as well progress such sclerosis, myasthenia gravis, acquired deficiency syndrome, 1 diabetes, sepsis, rheumatoid arthritis. Studies revealed regulation function suggesting application value treatment Keywords: irisin, FNDC5, cell, immunity,

Язык: Английский

Процитировано

0
Effect of zearalenone on the jejunum of weaned gilts through the Epac1/Rap1/JNK pathway DOI
Heng Liu, Lulu Ma,

Jiawei Fu

и другие.

Journal of Animal Science, Год журнала: 2024, Номер 102

Опубликована: Янв. 1, 2024

Zearalenone (ZEN) is a nonsteroidal estrogenic mycotoxin produced by Fusarium strains that harmful to the intestinal health of animals and widely present in contaminated crops. The objective this study was investigate potential therapeutic target ZEN-induced jejunal damage weaned gilts. Sixteen gilts either received basal diet or supplemented with 3.0 mg/kg ZEN 32-d experiment. results showed at concentration activated inflammatory response caused oxidative stress (P < 0.05). exposure resulted upregulation 0.05) Exchange protein directly cAMP 1/Ras-related protein1/c-Jun N-terminal kinase (Epac1/Rap1/JNK) signaling pathway jejunum vivo porcine epithelial cells vitro. cell viability, EdU-positive cells, mRNA expression B-cell lymphoma-2 (Bcl-2) were decreased, whereas reactive oxygen species production expressions Bcl-2-associated X (Bax) Cysteine-aspartic acid protease 3 (Caspase3) increased ZEN. However, Bcl-2 decreased Bax caspase3 after Epac1 blocked. These collectively indicated mg /kg induced via Epac1/Rap1/JNK pathway.

Язык: Английский

Процитировано

0