Design, synthesis, and evaluation of carboxylic acid-substituted celecoxib isosteres as potential anti-inflammatory agents

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 286, С. 117286 - 117286

Опубликована: Янв. 17, 2025

Язык: Английский

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Design, Synthesis, and Evaluation of Selective PDE4 Inhibitors for the Therapy of Pulmonary Injury

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Pulmonary inflammation is the main cause of lung injury. Phosphodiesterase 4 (PDE4) a promising anti-inflammatory target for treatment respiratory diseases. Herein, we designed and synthesized 43 compounds in two novel series benzimidazole derivatives as PDE4 inhibitors. Among them, compound A5 showed highly selective inhibition PDE4, good safety, liver microsomal stability vitro. administration remarkably attenuated inflammatory infiltration pathologic injury models acute mice chronic obstructive pulmonary disease (COPD) mice. In addition, enhanced sputum secretion, relieved cough mice, inhibited phosphorylation p38 MAP kinase, an important protein regulation Overall, A5, effective inhibitor without toxicity gastrointestinal reaction, may be potent candidate

Язык: Английский

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Nanocurcumin in myocardial infarction therapy: emerging trends and future directions

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 8, 2025

Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. Curcumin has been observed to significantly reduce pathological processes associated with MI. Its clinical application limited due its low bioavailability, rapid degradation, poor solubility. Advancements in nanotechnology can be used enhance therapeutic potentials nano-formulation enhances solubility, stability, allowing more precise delivery ischemic cardiac tissue. nanoparticles have successfully infarct size, maintain heart function by modulating essential molecular pathways liposomal formulations provide sustained release higher tissue penetration improved pharmacokinetics enhanced efficacy. Preclinical studies revealed that nanocurcumin drastically lower oxidative stress indicators, inflammatory cytokines, damage. Micelles composed polymers demonstrated high biocompatibility targeting capabilities increased cardio-protective effects. Research trials are for comprehensive analysis efficacy curcumin-based nano-therapeutics cardiovascular condition lowering risk

Язык: Английский

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Syk inhibitor attenuates lupus in FcγRIIb−/− mice through the Inhibition of DNA extracellular traps from macrophages and neutrophils via p38MAPK-dependent pathway

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 17, 2025

Abstract Spleen tyrosine kinase (Syk), an important hub of immune signaling, is activated by several signalings in active lupus which could be interfered Syk inhibitor but still not completely evaluated innate cells associated with activity. Hence, a (fostamatinib; R788) was tested vivo using Fc gamma receptor-deficient (FcγRIIb −/− ) mice and vitro (macrophages neutrophils). After 4 weeks oral inhibitor, 40 week-old FcγRIIb (a full-blown model) demonstrated less prominent parameters (serum anti-dsDNA, proteinuria, glomerulonephritis), systemic inflammation, as serum TNFa, IL-6, citrullinated histone H3 (CitH3), gut permeability defect, indicated FITC dextran assay, lipopolysaccharide (LPS), (1 → 3)-β-D-glucan (BG), extracellular traps (ETs) complex deposition spleens kidneys (immunofluorescent staining CitH3 immunoglobulin G) than placebo. Due to the spontaneous elevation LPS BG serum, plus (LPS + BG) used activate macrophages neutrophils. stimulation, neutrophils predominant abundance phosphorylated (Western blotting), pro-inflammatory responses (CD86 flow cytometry analysis, supernatant cytokines, ETs immunofluorescent, cytometry-based apoptosis). With RNA sequencing analysis western blotting, Syk-p38MAPK-dependent pathway suggested downregulating inflammatory pathways BG-activated Although both inhibitors against p38MAPK attenuated macrophage neutrophil WGP, apoptosis inhibition observed. These results that (fostamatinib) improved severity caused defect partly through Syk-p38MAPK anti-inflammation inhibited ET formation cytokine production from cells.

Язык: Английский

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Evaluation of Sapindus mukorossi Gaertn Flower Water Extract on In Vitro Anti-Acne Activity

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(5), С. 316 - 316

Опубликована: Апрель 28, 2025

Background: Sapindus mukorossi Gaertn is a deciduous tree with saponins as the main active ingredients and has been utilized in medicine cosmetic industries. Currently, investigations of S. mainly focus on pericarp seed kernel parts, while other parts are yet to be studied developed. This study aimed investigate anti-acne potential flower water extract (SMFW) by vitro experiments. Methods Results: The DPPH, ABTS, superoxide anion radical scavenging assay, FRAP assay revealed strong antioxidant activities SMFW. antibacterial activity SMFW against Cutibacterium acnes evaluated an inhibition diameter 14.08 ± 0.63 mm. Furthermore, significantly inhibited secretion pro-inflammatory cytokines (TNF-α, IL-6, IL-β) lipopolysaccharide (LPS)-stimulated THP-1 macrophages. Transcriptome analysis showed that treatment reversed 448 LPS-upregulated DEGs 349 LPS-downregulated DEGs, KEGG enrichment indicated might exert its anti-inflammatory effect via NOD-like receptor JAK-STAT signaling pathways. Conclusions: exhibited antioxidant, antibacterial, properties RNA-seq may alleviate inflammation regulating In summary, shown for efficacy can used natural raw material cosmetics.

Язык: Английский

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NJK14047 inhibition of p38 MAPK ameliorates inflammatory immune diseases by suppressing T cell differentiation

International Immunopharmacology, Год журнала: 2024, Номер 130, С. 111800 - 111800

Опубликована: Март 1, 2024

Язык: Английский

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Immunotherapeutic effects of de novo benzimidazole derivative and prebiotic bacterial levan against triple-negative breast tumors by harnessing the immune landscape to intercept the oncogenic transcriptome

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 289, С. 138844 - 138844

Опубликована: Дек. 18, 2024

Язык: Английский

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Negative Effect of Gst‐35 on the Health Span of Caenorhabditis elegans Through Lysosomal Dysfunction via the Pmk‐1 and Skr Genes

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

ABSTRACT As global life expectancy increases, the focus has shifted from merely extending lifespan to promoting healthy aging. GSTA1, GSTA2, and GSTA3 (GSTA1‐3), members of alpha class glutathione S‐transferases, are involved in diverse biological processes, including metabolism immune regulation, highlighting their potential influence on human health span lifespan. In this study, we employed Caenorhabditis elegans as a model organism investigate role gst‐35 , an ortholog mammalian GSTA1‐3, Our results demonstrated that overexpression detrimental effects multiple physiological functions nematodes. Specifically, significantly reduced lifespan, impaired development growth, substantially diminished reproductive capacity, physical fitness, stress resistance. contrast, knockout partially enhanced fitness Comprehensive RNA‐sequencing transcriptome analysis revealed disrupted metabolic homeostasis induced lysosomal dysfunction. These were mediated through activation pmk‐1 signaling pathway suppression skr genes, which collectively aging processes. findings illuminate complex provide valuable insights into molecular mechanisms underlying aging, offering targets for interventions aimed at span.

Язык: Английский

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The prognostic effect and mechanism of erysipelas in cancer-associated lymphedema

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 14, 2025

Lymphedema is a chronic condition that can follow cancer treatment, and liposuction has been shown to be an effective approach for reducing limb volume in advanced cases. However, recurrence rates vary widely, with prior erysipelas identified as potentially significant factor influencing prognosis. This study aimed identify key risk factors following patients cancer-associated secondary lymphedema, develop predictive nomogram model, investigate the molecular mechanisms by which previous may affect recurrence. In retrospective analysis of 1,016 patients, multivariate logistic regression propensity score matching four independent factors, namely, erysipelas, hyperlipidemia, severe distal edema, older age, showing strongest association poor outcomes (OR 3.98; 95% CI: 2.81–5.69). A validated demonstrated high accuracy (C-index 0.757, Brier 0.176) net clinical benefit estimating risk. The supports personalized treatment strategies, improving patient outcomes. Transcriptome sequencing further revealed exacerbates lymphedema through inflammation, tissue remodeling, metabolic dysregulation, suggesting potential therapeutic targets.

Язык: Английский

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The relationship mammalian p38 with human health and its homolog Hog1 in response to environmental stresses in Saccharomyces cerevisiae

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Март 10, 2025

The mammalian p38 MAPK pathway plays a vital role in transducing extracellular environmental stresses into numerous intracellular biological processes. have been linked to variety of cellular processes including inflammation, cell cycle, apoptosis, development and tumorigenesis specific types. has implicated the many human diseases become target for treatment cancer. Although extensively studied, questions still await clarification. More comprehensive understanding will provide new possibilities diseases. Hog1 S. cerevisiae is conserved homolog cells HOG signaling studied. deep help clues clarifying pathway, thereby furthering our relationship between disease. In this review, we elaborate functions while also analyzing how regulates response stresses. 1, various cells.2, health.3, as Saccharomyces . cells. 2, health. 3,

Язык: Английский

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