Toxicology and Applied Pharmacology, Journal Year: 2024, Volume and Issue: 495, P. 117199 - 117199
Published: Dec. 8, 2024
Language: Английский
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 14, 2025
Background Erectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood. Objective This study aims to explore role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate therapeutic potential Fasn inhibitor C75. Materials methods function was assessed by determining intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, followed collection cavernous tissue for transcriptomic non-targeted metabolomic analyses. In vitro , concentration 10 -6 M angiotensin II (Ang II) applied rat aortic endothelial cells (RAOECs) establish model hypertension. vivo spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections C75 at dose 2 mg/kg once week. After five weeks treatment, erectile assessed, penile tissues harvested further analysis. Molecular protein expression using Western blotting, qRT-PCR, immunofluorescence staining, immunohistochemistry. Results SHR exhibited ED, indicated reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum showed elevated fibrosis dysfunction. Additionally, increased NLRP3 inflammasome, Caspase-1, GSDMD, pro-inflammatory cytokines IL-1β IL-18 observed. Multi-omics analysis revealed significant enrichment lipid metabolic pathways, identified as hub gene. siFasn enhanced antioxidant markers Nrf2 HO-1, ROS accumulation, suppressed GSDMD levels. treatment restored reversed dysfunction, accompanied decreased oxidative stress pyroptosis cavernosum. Conclusion These findings suggest that inhibition may offer promising strategy alleviating suppressing inflammasome-dependent cell via activation Nrf2/HO-1 pathway.
Language: Английский
Citations
1
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114123 - 114123
Published: Jan. 29, 2025
Language: Английский
Citations
1
BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)
Published: Jan. 22, 2025
Oxidative stress is associated with functional bowel disorders. The Balance Score (OBS) used to represent the overall level of oxidative experienced by an individual. Sex differences are exhibited in occurrence constipation and diarrhea. This population-based study aimed examine association between OBS, constipation, diarrhea, among adults United States (US), stratified sex. Using data from National Health Nutrition Examination Survey (NHANES) database spanning 2007 2010, a cross-sectional including 4,462 participants (2,386 males 2,076 females) was performed assess relationship adult men women US. Constipation diarrhea were identified according frequency stool type, as outlined Bowel Questionnaire. independent variable OBS based on 20 types dietary lifestyle components. We conducted binary logistic regression subgroup analysis sex, univariate analysis; restricted cubic spline (RCS) illustrate abnormal health. After adjusting for all covariates, multivariate revealed that negatively correlated [odds ratios (OR) (95% confidence intervals (CI)): 0.937 (0.888, 0.988), P = 0.017], females [OR (95%CI): 0.951 (0.916, 0.987), 0.009]. RCS negative linear trend (P non-linearity 0.63), well > 0.05). current found correlation risk males, along females. stress, gut microbiota, sex may be intestinal dysfunction. These findings suggest antioxidant-rich modifications effective strategy preventing
Language: Английский
Citations
0
Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 398 - 398
Published: March 27, 2025
Hydroxytyrosol (HT), a principal bioactive phytochemical abundant in Mediterranean dietary sources, has emerged as molecule of significant scientific interest owing to its multifaceted health-promoting properties. Accumulating evidence suggests that HT’s therapeutic potential metabolic disorders extends beyond conventional antioxidant capacity encompass mitochondrial regulatory networks. This review synthesizes contemporary from our systematic investigations and the existing literature delineate comprehensive modulatory effects on homeostasis. We systematically summarized impact HT dynamics (fusion/fission equilibrium), biogenesis energy metabolism, mitophagy, inter-organellar communication with endoplasmic reticulum, microbiota–mitochondria crosstalk. Through this multidimensional analysis, we established homeostasis modulator applications syndrome (MetS) related pathologies including type 2 diabetes mellitus, obesity-related dysfunction, dyslipidemia, non-alcoholic steatohepatitis, hypertension-related complications. Moreover, further discussed translational challenges research, emphasizing imperative for direct target identification, mitochondrial-targeted delivery system development, combinatorial strategies. Collectively, provides mechanistic framework advancing research accelerating clinical implementation MetS diseases.
Language: Английский
Citations
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Journal of Functional Foods, Journal Year: 2025, Volume and Issue: 127, P. 106789 - 106789
Published: April 1, 2025
Language: Английский
Citations
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Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106502 - 106502
Published: April 1, 2025
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: April 8, 2025
The "Anchang" Group Prescription (ACZF), based on the traditional Bai Tou Weng Decoction and Si Jun Zi Decoction, has demonstrated clinical efficacy in alleviating symptoms of radiation enteritis (RE). Nevertheless, precise active components their underlying molecular mechanisms ACZF's effect RE require further elucidation. This investigation seeks to delineate explore by which ACZF mitigates RE, utilizing both network pharmacology experimental approaches provide a solid theoretical base for subsequent research applications. Utilizing pharmacology, this constructed comprehensive "drug-active ingredient-target gene-disease" model leveraging resources such as TCMSP, SwissTargetPrediction, GeneCard, OMIM. Cytoscape 3.8.2 along with STRING database were instrumental developing protein-protein interaction (PPI) identification pivotal targets. Functional enrichment analyses, including Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathways, conducted via DAVID database. Experimentally, mouse was induced X-ray exposure assess physiological pathological responses. Parameters measured included body weight, survival rate, incidences diarrhea, hematochezia; histological assessments involved hematoxylin eosin (H&E) Masson's trichrome staining examine morphological alterations collagen deposition colonic tissues. Levels cytokines interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α) quantified using enzyme-linked immunosorbent assays (ELISA). Additionally, immunohistochemistry (IHC) Western blotting (WB) employed evaluate expression tight junction proteins zonula occludens-1 (ZO-1) claudin-1, well linked PI3K/AKT pathway. Key bioactive constituents treating include quercetin, kaempferol, isorhamnetin, luteolin, core target SRC, STAT3, AKT, HSP90AA1, EGFR. Involved signaling pathways PI3K/AKT, RAP1, MAPK. In vivo results revealed that mice treated showed enhanced survival, increased extended colon lengths compared controls. Although Masson no significant differences, H&E indicated radiation-induced mucosal damage, extensive ulcer formation, inflammatory cell infiltration, crypt structure destruction, epithelial layer injury, could all be ameliorated ACZF. Notable reductions observed TNF-α, IL-1β, IL-6 levels, while IL-10 levels saw rise. There also marked increase ZO-1 claudin-1. WB analyses activation pathway significantly curtailed ACZF, lowering phosphorylation within Concurrent administration PI3K activator YS-49 reversed inhibitory effects mitigated impacts TJ protein cytokine highlighting critical role mediating therapeutic RE. alleviates inhibiting activation, reducing inflammation, preserving intestinal integrity.
Language: Английский
Citations
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Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 476 - 476
Published: April 16, 2025
Tyrosol (Tyr), hydroxytyrosol (TH), and 3,4-Dihydroxyacetophenone (3,4-DHAP) are three phenolic compounds naturally present in plants that have attracted considerable research attention due to their potent antioxidant, anti-inflammatory, anticancer, cardiovascular protective properties. In recent years, mounting evidence has indicated these hold broad potential both disease prevention treatment. This paper reviews the chemical structures synthetic methods of Tyr, HT, 3,4-DHAP, as well multifaceted effects on human health, particularly roles mechanisms antioxidation, anti-inflammation, protection, neuroprotection, anticancer activity. addition, this explores future prospects current challenges associated with application—such low bioavailability long-term safety concerns—and proposes directions for further investigation.
Language: Английский
Citations
0
Nutrients, Journal Year: 2025, Volume and Issue: 17(9), P. 1421 - 1421
Published: April 23, 2025
Background/Objectives: Ovarian aging represents a critically important aspect of female senescence. It not only denotes the loss fertility but is also accompanied by series physiological changes and other organs. Hydroxytyrosol (HT), natural polyphenolic phytocompound, has been demonstrated to exhibit remarkable effects in regulating autophagy, inflammation, process. However, relationship between HT ovarian aging, as well specific underlying mechanisms, remains poorly understood. Methods: In this study, network pharmacology, molecular docking, dynamics simulation were employed explore regulatory effect on inflammaging via autophagy-targeted mechanisms. Results: Through pharmacology analysis, study successfully identified 10 hub genes associated with regulation. Notably, four out top five found be closely related autophagy pathways. Further investigation revealed pivotal role ATG7: may regulate through activating FIP200 (focal adhesion kinase family interacting protein 200 kD)-dependent non-canonical selective pathway. The results docking indicated that ATG7 strong binding ability HT. Molecular further verified stability two. Conclusions: By possible pathway for was explored, providing cues research.
Language: Английский
Citations
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Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: May 12, 2025
Diquat is a widely used bipyridyl herbicide that extensively applied in agricultural production and water management due to its high efficacy weed control. However, environmental persistence the toxic effects it induces have raised widespread concern. Studies show primarily enters body through digestive tract, leading poisoning. The core mechanism of toxicity involves reactive oxygen species (ROS)-induced oxidative stress, which not only directly damages intestinal barrier function but also exacerbates inflammation systemic by disrupting balance gut microbiota normal metabolic products. This review systematically summarizes physicochemical properties Diquat, with focus on analyzing mechanisms tissue structure, function, after tract exposure. aim provide theoretical support for deeper understanding Diquat’s tract-centered characteristics, laying scientific foundation development effective interventions protective strategies against toxicity.
Language: Английский
Citations
0