Experimental Eye Research, Journal Year: 2024, Volume and Issue: 249, P. 110130 - 110130
Published: Oct. 18, 2024
Language: Английский
Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)
Published: March 28, 2025
Language: Английский
Citations
0
European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)
Published: April 11, 2025
Airway remodeling in bronchial asthma can be inhibited by disrupting the epithelial mesenchymal transition (EMT) of activated airway cells. Exosomes, as key mediators intercellular communication, have been implicated pathophysiology asthma-related inflammation, remodeling, and hyperresponsiveness. This study aimed to investigate role M2 macrophage-derived exosomes (M2φ-exos) modulating TGF-β1-induced EMT (BEAS-2B) cells elucidate underlying molecular mechanism, if any. THP-1 were induced differentiate into macrophages via phorbol 12-myristate 13-acetate (PMA) IL-4. Exosomes subsequently isolated purified ultracentrifugation. M2φ-exos expression was characterized protein marker levels, transmission electron microscopy imaging, nanoparticle tracking analysis. BEAS-2B exposed determine latter's effects. successfully differentiated macrophages, confirmed vitro flow cytometry. The presented typical cup-shaped structures expressed CD81 TSG101. TGF-β1 induction altered morphological characteristics TGF-βRI/Smad2/3 signaling pathway, leading increased Snail, Vimentin Collagen 1 decreased E-cadherin. After exosome or SB431542 induction, reversed. GW4869, an release inhibitor, exhibited ability block beneficial effects exosomes. M2Φ-exos through pathway. novel insight may important implications for asthma, particularly addressing remodeling.
Language: Английский
Citations
0
Food Frontiers, Journal Year: 2025, Volume and Issue: unknown
Published: April 28, 2025
ABSTRACT Benign prostate hyperplasia (BPH) is characterized by abnormal epithelial and stromal cell growth, which leads to bladder outlet obstruction (BOO) lower urinary tract symptoms (LUTS). BPH pathogenesis involves key signaling pathways, including androgen/androgen receptor (AR) transforming growth factor‐beta (TGF‐β)/Smad, contribute proliferation, transformation, epithelial–mesenchymal transition (EMT). To date, the effect of Hovenia dulcis honey (HH) on has not been reported. Herein, in vivo vitro models were used determine whether HH therapeutic effects its underlying mechanisms, if present. evaluate anti‐BPH vivo, mice treated with testosterone propionate (TP; 10 mg/kg, s.c.), finasteride (Fi; i.p.), or (600 p.o.) for 4 weeks. Additionally, efficacy was evaluated using a dihydrotestosterone (DHT)‐stimulated RWPE‐1 model. significantly reduced size, thickness, markers AR (prostate‐specific antigen [PSA], proliferating nuclear [PCNA], DHT) as well exhibited anti‐inflammatory lowering expression inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α) inhibited EMT process decreasing α‐smooth muscle actin (α‐SMA), neural cadherin (N‐cadherin), vimentin levels while restoring (E‐cadherin) expression. These findings suggest that inhibits androgen/AR TGF‐β/Smad pathways may offer novel approach treatment.
Language: Английский
Citations
0
PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(5), P. e1012382 - e1012382
Published: May 2, 2025
The link between p53 tumor suppressive functions and organismal lifespan is multifaceted. Its DNA-repair mechanism longevity-enhancing while its role in cellular senescence pathways induces pro-aging phenotypes. To understand how may regulate lifespan, cross-species genotype-phenotype (GP) studies of the DNA-binding domain (DBD) have been used to assess correlation amino acid changes lifespan. Amino non-DNA-binding regions such as transactivation (TAD), proline-rich (PRD), regulatory (REG), tetramerization (TET) are largely unexplored. In addition, existing GP tools SigniSite do not account for phylogenetic relationships aligned sequences correlating genotypic differences phenotypes identify phylogenetically significant, longevity-correlated residues full-length alignments, we developed a Python- R-based workflow, Relative Evolutionary Scoring (RES). While RES-predicted longevity-associated (RPLARs) concentrated primarily DBD, PRD, TET, REG domains also house RPLARs. yeast functional assay enrichment reveals that RPLARs be dispensable p53-mediated transactivation, PEPPI Rosetta-based protein-protein interaction prediction suggests stability interfaces complexes. With experimental validation RPLARs’ roles stability, transactivity, involvement senescence-regulatory pathways, can gain crucial insights into mechanisms underlying dysregulated suppression accelerated aging.
Language: Английский
Citations
0
Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)
Published: April 18, 2024
Abstract Background TGF-β1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis. Aim This study aimed to evaluate kidney protective potentials silymarin (SM) exosomes mesenchymal stem cells against nephrotoxin thioacetamide (TAA) rats. Methods 32 female rats were randomly assigned into four groups: control group, TAA + SM Exosomes group. The homogenates from all groups examined for expression levels TGF-β receptors I II using real-time PCR, collagen type CTGF proteins ELISA, nuclear SMAD2/3/4, cytoplasmic SMAD2/3, SMAD4 western blot technique. Results Compared injection resulted a significant increase serum urea creatinine, gene TβRI TβRII, protein both proteins, SMAD2/3 complex, SMAD2/3/4 (p-value < 0.0001), with significantly decreased co-SMAD partner, 0.0001). Those effects reversed considerably treatment groups, superiority exosomal regarding SMAD gene, I, returning near-control values > 0.05). Conclusion Using vitro vivo experimental approaches, research discovered reno-protective role BM-MSCs after thioacetamide-induced fibrosis rats, advantage exosomes.
Language: Английский
Citations
3
Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)
Published: Aug. 20, 2024
The epigenetic status of patients 6-month post-COVID-19 infection remains largely unexplored. existence long-COVID, or post-acute sequelae SARS-CoV-2 (PASC), suggests potential long-term changes. Long-COVID includes symptoms like fatigue, neurological issues, and organ-related problems, regardless initial severity. mechanisms behind long-COVID are unclear, but virus-induced changes could play a role. Our study explores the lasting impacts infection. We analyzed genome-wide DNA methylation patterns in an Italian cohort 96 6 months after COVID-19 exposure, comparing them to 191 healthy controls. identified 42 CpG sites with significant differences (FDR < 0.05), primarily within islands gene promoters. Dysregulated genes highlighted links glutamate/glutamine metabolism, which may be relevant PASC symptoms. Key significance effects include GLUD1, ATP1A3, ARRB2. Furthermore, Horvath's clock showed slight age acceleration patients. also observed substantial increase stochastic mutations (SEMs) group, implying drift. SEM analysis 790 affected genes, indicating dysregulation pathways related insulin resistance, VEGF signaling, apoptosis, hypoxia response, T-cell activation, endothelin signaling. provides valuable insights into consequences COVID-19. Results suggest possible associations accelerated aging, drift, disruption critical biological linked immune vascular health. Understanding these crucial for elucidating complex developing targeted therapeutic interventions.
Language: Английский
Citations
3
Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2479 - 2479
Published: July 7, 2024
Chemoresistance is a major obstacle in cancer treatment, often leading to disease progression and poor outcomes. It arises through various mechanisms such as genetic mutations, drug efflux pumps, enhanced DNA repair, changes the tumor microenvironment. These processes allow cells survive despite chemotherapy, underscoring need for new strategies overcome resistance improve treatment efficacy. Crizotinib, first-generation multi-target kinase inhibitor, approved by FDA of ALK-positive or ROS1-positive non-small cell lung (NSCLC), refractory inflammatory (ALK)-positive myofibroblastic tumors (IMTs) relapsed/refractory anaplastic large lymphoma (ALCL). Crizotinib exists two enantiomeric forms: (R)-crizotinib its mirror image, (S)-crizotinib. assumed that R-isomer responsible carrying out reviewed here The S-isomer, on other hand, shows strong inhibition MTH1, an enzyme important repair mechanisms. Studies have shown crizotinib effective multi-kinase inhibitor targeting kinases c-Met, native/T315I Bcr/Abl, JAK2. Its mechanism action involves competitive ATP binding allosteric inhibition, particularly at Bcr/Abl. showed synergistic effects when combined with poly ADP ribose polymerase (PARP), especially ovarian harboring BRCA gene mutations. In addition, targets critical vulnerability many p53-mutated cancers. Unlike wild-type counterpart, p53 mutant promotes survival. can cause degradation mutant, sensitizing these DNA-damaging substances triggering apoptosis. Interestingly, reports demonstrated exhibits anti-bacterial activity, Gram-positive bacteria. Also, it active against drug-resistant strains. summary, exerts anti-tumor several mechanisms, including restoration sensitivity. potential combination therapies emphasized, cancers high prevalence triple-negative breast (TNBC) high-grade serous (HGSOC).
Language: Английский
Citations
2
Cancer Reports, Journal Year: 2024, Volume and Issue: 7(8)
Published: Aug. 1, 2024
Integrin-Binding Sialoprotein (IBSP) has been implicated in tumor progression across various cancers. However, the specific role of IBSP breast cancer remains underexplored. There is a need to investigate mechanisms by which influences and its potential as therapeutic target.
Language: Английский
Citations
2
Cell Regeneration, Journal Year: 2024, Volume and Issue: 13(1)
Published: Nov. 28, 2024
Abstract Human stem cells are undifferentiated with the capacity for self-renewal and differentiation into distinct cell lineages, playing important role in development maintenance of diverse tissues organs. The microenvironment provides crucial factors components that exert significant influence over determination fate. Among these factors, cytokines from transforming growth factor β (TGFβ) superfamily, including TGFβ, bone morphogenic protein (BMP), Activin Nodal, have been identified as regulators governing differentiation. In this review, we present a comprehensive overview pivotal roles played by TGFβ superfamily signaling human embryonic cells, somatic induced pluripotent cancer cells. Furthermore, summarize latest research advancements family various cell-based therapy, discussing their potential clinical applications therapy regeneration medicine.
Language: Английский
Citations
2
Molecules, Journal Year: 2024, Volume and Issue: 30(1), P. 20 - 20
Published: Dec. 25, 2024
Diabetic nephropathy (DN) is a common and serious complication of diabetes mellitus major cause end-stage renal disease (ESRD). Renal fibrosis, which corresponds to excessive deposition extracellular matrix leads scarring, characteristic feature the various progressive stages DN. It can trigger pathological processes leading activation autophagy, inflammatory responses vicious circle oxidative stress inflammation. Although it known that DN be alleviated by mechanisms linked antioxidants, reducing inflammation improving how improve fibrosis using natural polyphenols needs studied further. Nowadays, polyphenolic compounds with excellent safety efficacy are playing an increasingly important role in drug discovery. Therefore, this review reveals multiple associated DN, as well different signaling pathways (including TGF-β/SMAD, mTORC1/p70S6K, JAK/STAT/SOCS Wnt/β-catenin) potential fibrotic niche. In parallel, we summarize types their pharmacodynamic effects, finally evaluate use modulate relevant targets pathways, providing research directions for summary, problem long-term monotherapy resistance reduced polyphenols, while incidence toxic side effects. addition, inhibitors identified through these offering avenues pharmacological treatment multisite fibrosis.
Language: Английский
Citations
1