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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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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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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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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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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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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Regulatory dynamics of Nanog in chondrocyte dedifferentiation: role of KLF4/p53 and p38/AKT signaling

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Март 11, 2025

Язык: Английский

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Plasmodium Infection Modulates Host Inflammatory Response through circRNAs during the Intracellular Stage in Red Blood Cells

ACS Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

The integration of RNA- and DNA-based assays enables the investigation disease dynamics, specifically assessing role asymptomatic or subclinical infections in malaria transmission. Circular RNAs (circRNAs), a distinct category noncoding RNAs, are implicated numerous pathogenic mechanisms. As now, research has yet to explore circRNAs' function infection. findings revealed that Plasmodium infection upregulated 60 circRNAs downregulated 71 BALB/c mice. We selected 11 differentially expressed (DE) according prediction target miRNA-mRNA coding protein, these were further confirmed by validation experiments. IRESfinder, GO, KEGG evaluations indicated 7 DE possess protein-coding potential enriched MAPK signaling cascade. In P.y17XL-infected mouse models, substantiated dynamic characteristics correlated with inflammation, NF-κB cascades activated, also contributing inflammatory reaction during This study establishes Plasmodium-induced circRNA expression as novel mechanism which parasite modulates host immune signaling, advancing understanding Plasmodium–host cell interactions. addition, 42 found normal mice, 25 discovered excluding 1238 shared changes profile host, altered involved response possibly regulates reverse splicing pre-mRNA m6A modification RNA, inducing production host.

Язык: Английский

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Electroacupuncture Attenuates Intestinal Barrier Disruption via the α7nAChR-Mediated HO-1/p38 MAPK/NF-κB Pathway in a Mouse Model of Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized, Single-Blind, Controlled Trial

Biomedicines, Год журнала: 2025, Номер 13(4), С. 802 - 802

Опубликована: Март 27, 2025

Background: Gut barrier integrity plays a crucial role in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Electroacupuncture (EA) at ST-36 can ameliorate inflammatory responses via stimulating α7 nicotinic acetylcholine receptor (α7nAChR), but whether EA is effective preserving intestinal MAFLD has not been exactly illustrated. This investigation explored potential protection mechanisms targeting dismantled gut MAFLD. Methods: C57BL/6 mice were randomly allocated into several subgroups: control (CON), high-fat diet (HFD), HFD with EA, and α7nAChR inhibitor α-BGT, HO-1 knockout (KO). Body weight, visceral fat index, histopathological examination intestine determined. Serum biological indexes evaluated through corresponding kits. Furthermore, expressions HO-1, α7nAChR, barrier-associated proteins, molecular tissues assessed Western blot, RT-qPCR, immunohistology, or immunofluorescence examination. Results: treatment decreased body index gain mitigated function injury abnormal lipid indexes, exhibiting less severity hepatic steatosis, fibrosis, inflammation Lower permeability, epithelial disruption, upregulation tight junction proteins after suggested protective effects attenuating dysfunction. These abolished by α-BGT deletion. Mechanistically, markedly enriched expression phosphorylated p38 MAPK/NF-κB activation, which was lost KO treatment. Conclusions: The may be attributed to preserved barrier, thereby alleviating systemic preventing subsequent hits, where α7nAChR-mediated HO-1/p38 pathway maintain homeostasis.

Язык: Английский

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Laboratory Investigation of Chemical Constituents and Anti-inflammatory Activity of Putranjiva roxburghii Hexane Fraction Based on Combined Docking and Molecular Dynamics Simulation Study

Chemistry Africa, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Язык: Английский

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