Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1204 - 1204

Published: Jan. 30, 2025

Nitric oxide synthases (NOS) are crucial enzymes responsible for the production of nitric (NO), a signaling molecule with essential roles in vascular regulation, immune defense, and neurotransmission. The three NOS isoforms, endothelial (eNOS), neuronal (nNOS), inducible (iNOS), tightly regulated by inflammatory mediators cellular pathways. While physiological NO is vital maintaining homeostasis, dysregulated activity contributes to pathogenesis numerous diseases, including cardiovascular disorders, neurodegenerative conditions, cancer. Recent advances understanding molecular mechanisms regulation have unveiled novel therapeutic opportunities, isoform-specific modulators, upstream pathways, nanotechnology-enhanced delivery systems. This review highlights these advancements, offering insights into how targeting its regulatory network can enable precise effective strategies managing inflammation-driven pathologies.

Language: Английский

---

Mechanism of Traditional Chinese medicine extract in the treatment of diabetic erectile dysfunction

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119332 - 119332

Published: Jan. 1, 2025

Language: Английский

---

Identifying potential therapeutic targets for prostate cancer with mediating role in tumor immunity

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Background Prostate cancer (PCa) is a leading malignancy with rising global incidence, posing significant challenges in treatment. The immunosuppressive tumor microenvironment (TME) CRPC major barrier to effective immunotherapy. Identifying therapeutic targets that modulate the immune response within TME crucial for advancing PCa Materials and Methods In this study, we employed Mendelian randomization (MR) investigate causal relationships between gene expression of blood proteins risk. We utilized cis-eQTL data from eQTLGen Consortium cell phenotype NHGRI-EBI GWAS Catalog. Our analysis included discovery validation cohorts, totaling over 800,000 individuals. Colocalization was performed confirm genetic associations, mediation MR used explore mediating role immunity. Drug prediction molecular docking were applied assess potential identified as druggable candidates. Results 557 associated cohort, 86 remaining an independent cohort. Mediation revealed nine mediated impact cells on PCa. confirmed causality five proteins, which further supported by phenome-wide association studies (PheWAS) protein-protein interaction (PPI) networks. Molecular demonstrated strong binding affinity drugs these targets. Conclusions This study drug prostate response. These may expedite development personalize medicine, potentially enhancing treatment efficacy reducing side effects.

Language: Английский

---

p16INK4a Aggravated Sepsis-associated Cardiac Injury by Inhibiting the PI3K/AKT Pathway and Inducing Redox Imbalance

Journal of Cardiovascular Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

---

Network Pharmacology and Molecular Analysis of Mechanisms underlying the therapeutic effects of Rhubarb in treating Atherosclerosis and Abdominal Aortic Aneurysm

Heliyon, Journal Year: 2025, Volume and Issue: 11(4), P. e41906 - e41906

Published: Jan. 23, 2025

The aim of this study was to systematically investigate the effects and mechanisms Rhubarb in treatment Atherosclerosis (AS) Abdominal Aortic Aneurysm (AAA) by utilizing network pharmacology molecular docking techniques. TCMSP systematic database utilized search for active chemical components Rhubarb. Disease-related targets were retrieved from GEO dataset Disgenet database. Gene interactions identify common with AS/AAA, interaction networks constructed using Cytoscape 3.9.1. Protein-protein (PPI) core STRING GO KEGG pathway enrichment analysis performed DAVID. Molecular is used assess potential target-active compound interactions. In our study, 16 compounds screened Rhubarb, along 310 targets. Additionally, 110 AS/AAA target genes out. Topological PPI protein yielded 23 targets, biological functions signaling pathways further investigated. indicated that may be effective treating through processes such as lipids, atherosclerosis, extracellular matrix catabolism, collagenolytic metabolic processes, environment. Five pharmacological also identified: TNF, IL-1β MMP9, TP53, PPARG. showed a strong binding ability between This successfully predicted functions, associated AS/AAA. addition, identified ingredients can source drug screening.

Language: Английский

---

Higher hemoglobin levels are associated with impaired left ventricular global strains in metabolic syndrome: a 3.0 T CMR feature tracking study

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: March 17, 2025

Metabolic syndrome (MetS) is a known contributor to increased cardiovascular risk and all-cause mortality. Recent literatures suggested that higher hemoglobin (Hb) levels were associated with Mets, left ventricular (LV) dysfunction adverse events in general population. This study aimed assess the associations between Hb LV global strains patients MetS. A retrospective analysis included 254 MetS 78 sex-, age-, Hb-matched controls. The stratified into five groups based on levels: anemia, low-normal Hb, moderate-normal high-normal high Hb. radial, circumferential, longitudinal (LVGRS, LVGCS, LVGLS, respectively) measured using cardiac magnetic resonance feature tracking technique. Associations evaluated multiple linear regression, restricted cubic spline (RCS), subgroup analyses. After full adjustment, from three directions (LVGRS: β = − 4.943, 95% CI 7.673 2.213; LVGCS: 2.341, 3.608 1.074; LVGLS: −2.797, 4.049 1.546, all p < 0.05) significantly reduced than those their respective groups. Full adjusted RCS plots revealed inverted L-shaped strains, significant reductions observed above 143 g/L (all for nonlinearity 0.05). Subgroup analyses indicated more pronounced obesity 0.005 [95% 0.087 0.097] versus −0.087 0.145 0.030]; −0.006 0.045 0.034] −0.048 0.075 0.021]; −0.011 0.053 0.032] −0.063 0.089 0.036] non-obese obese patients; interaction Higher are severe patients, particularly obesity. Targeted monitoring management of may help mitigate further deterioration function.

Language: Английский

---

Biomimetic gold nano-modulator for deep-tumor NIR-II photothermal immunotherapy via gaseous microenvironment remodeling strategy

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 18, 2025

Effective immunotherapeutic treatment of solid tumors has been greatly challenged by the complex hostile tumor immunosuppressive microenvironment (TIME), which typically involves hypoxia and immunosuppression. Herein, a multifunctional biomimetic gold nano-modulator (denoted as GNR-SNO@MMT) was developed to realize efficient second near-infrared (NIR-II) photothermal immunotherapy via targeting deep penetration, vascular normalization immune reprogramming. NIR-II agent nanorods (GNR) were grafted with thermosensitive S-nitrosothiol (SNO) donors camouflaged tumor-penetrating peptide tLyp-1-modified macrophage membrane (MM) yield GNR-SNO@MMT. The engineered coating increased capacity for inflammatory tropism aided GNR-SNO@MMT in ablating together laser irradiation. Moreover, hyperthermia-stimulated nitric oxide (NO) release situ acted gas immunomodulator effectively enhance blood perfusion reprogram TIME multiple functions (e.g., decreasing PD-L1, repolarizing tumor-associated macrophages, revitalizing cytotoxic T cells). Ultimately, inhibition rate against 4T1 mouse mammary model mediated plus 94.7% 2.4-fold CD8+ cells infiltrated into than that untreated counterpart. provides an effective novel photoimmunotherapy candidate deep-sited through reconfiguration NO-involved nanomedicine external assistance.

Language: Английский

---

Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 439 - 439

Published: March 19, 2025

Cardiovascular diseases (CVDs), which include multiple disorders of the heart and blood vessels, are leading causes death. Nitric oxide (NO) is a vasodilator that regulates vascular tension. Endogenous NO produced via L-arginine–nitric synthase (NOS) pathway. In conditions cardiovascular dysfunction, NOS activity impaired, to deficiency. turn, reduction in bioactivity exacerbates pathogenesis CVDs. Exogenous intake inorganic nitrate supplements endogenous production nitrate–nitrite–NO pathway maintain supply. Salivary glands play an essential role conversion NO, with approximately 25% circulating being absorbed secreted into saliva. As result, salivary concentrations can exceed by more than tenfold. This recycled saliva serves as reservoir for performs NO-like functions when insufficient. this review, we summarize emerging benefits dietary CVDs, particular focus on salivary-gland-mediated recirculation maintaining bioavailability homeostasis. Salivary-gland-mediated provides novel perspective potential intervention

Language: Английский

---

Current knowledge on the mechanisms underpinning vasculogenic mimicry in triple negative breast cancer and the emerging role of nitric oxide

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 186, P. 118013 - 118013

Published: March 28, 2025

Language: Английский

---

Association between the atherogenic index of plasma and the systemic immuno-inflammatory index using NHANES data from 2005 to 2018

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 2, 2025

Language: Английский

---